Clinical Trials Register

Summary
EudraCT Number:	2018-001781-41
Sponsor's Protocol Code Number:	NVALT1asbestosis
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-11-01
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2018-001781-41

A.3

Full title of the trial

Evaluation of safety and tolerability of pirfenidone in asbestosis, a multicenter study

Evaluatie van de veiligheid en tolerantie van Pirfenidone bij asbestose, een multicenter studie

A.3.1

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

Evaluation of safety and tolerability of pirfenidone in pulmonary scarring due to asbestos, a multicenter study

Evaluatie van de veiligheid en tolerantie van Pirfenidone bij littekens in de long door asbest, een multicenter studie

A.3.2

Name or abbreviated title of the trial where available

PIRF-asbestosis

PIRF-asbestose

A.4.1

Sponsor's protocol code number

NVALT1asbestosis

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	Nederlandse Vereniging van Artsen voor longziekten en Tuberculose
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Roche BV
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Nederlandse Vereniging van Artsen voor longziekten en Tuberculose
B.5.2	Functional name of contact point	J.R.Miedema
B.5.3	Address:
B.5.3.1	Street Address	Doctor Molewaterplein 40
B.5.3.2	Town/ city	rotterdam
B.5.3.3	Post code	3015 GD
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031107040704
B.5.6	E-mail	j.miedema@erasmusmc.nl

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	Yes
D.2.1.1.1	Trade name	Esbriet (Pirfenidone)
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/04/ 241
D.3 Description of the IMP
D.3.1	Product name	Pirfenidone
D.3.2	Product code	SAP-10163800
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PIRFENIDONE
D.3.9.1	CAS number	53179-13-8
D.3.9.2	Current sponsor code	RO0220912
D.3.9.3	Other descriptive name	Esbriet
D.3.9.4	EV Substance Code	SUB09907MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	801
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

asbestosis

asbestose

E.1.1.1

Medical condition in easily understood language

pulmonary scars due to asbestos

littekens in de long door asbest

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

to investigate the safety and tolerability of pirfenidone in asbestosis patients

de veiligheid en verdraagzaamheid van pirfenidon bij asbestose patienten onderzoeken

E.2.2

Secondary objectives of the trial

Secondary objective is describing the effect of pirfenidone

secundaire doel is het beschrijven van het effect van pirfenidon

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients (40-85 years) with confirmed asbestosis by Dutch NVALT IPF expertise-panel (History of asbestos exposition with 15-30 years latency
AND pleural plaques OR asbestos fibers in pulmonary lavage OR asbestos fibers confirmed in lung biopsy), AND criteria 1-6

1. written informed consent
2. FVC ≥ 50% predicted, DLCO ≥ 25%
3. Minimal 6 minute walk test distance 150 meter
4. FEV1/FVC > 0.70
5. Documented disease progression in 3-6 months (absolute of relative FVC decrease > 5% in 3-6 months or absolute or relative DLCOc decrease > 10% in 3-6 months, or decrease ≥ 25 meter on 6 minute walk test in 3-6 months)

patienten (40-85 jaar) met bevestigde asbestose door het NVALT IPF expertisepanel (asbestinhalatie 15-30 jaar geleden EN pleurale plaques OF asbestvezels in longlavage of longbiopt) EN criteria 1 t/m 6

1. Geschreven geïnformeerde toestemming
2. FVC ≥ 50% voorspeld, DLCO ≥ 25%
3. Minimaal 6 minuten loop test, afstand 150 meter
4. FEV1/FVC > 0.70
5, Vastgelegde ziekte progressive binnen 3-6 maanden (Absolute of relatieve FVC afname > 5% binnen 3-6 maanden, of absolute of relatieve DLCO afname > 10% binnen 3-6 maanden, of afname ≥ 25 meter van de 6 minuten loop test binnen 3-6 maanden)

E.4

Principal exclusion criteria

1. current smoker
2. > 15% emphysema on HRCT thorax
3. >10mg prednisone daily or other immunosuppressant (MTX, azathioprine, cyclophosphamide)
4. malignancy
5. Hepatic impairment (History of hepatic impairment, elevation of transaminase enzymes, or the confirmation of any of the following liver function test criteria above the specified limits: Total bilirubin above the upper limit of normal (ULN), Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 × ULN, Alkaline phosphatase > 2.0 × ULN)
6. Renal impairment (GFR < 30 ml/min or dialysis)
7.Pregnancy
8.Concomitant use of a strong and selective inhibitor of CYP1A2 (Fluvoxamin, enoxacin)

1. actief roker
2. > 15% emphysema op HRCT thorax
3. >10mg prednison dagelijks of andere immunosuppresiva
4. Maligniteit
5. Leverfunctiestoornis (voorgeschiedenis met leverfunctiestoornis, bilirubine > bovenwaarde van normaal, ASAT of ALAT > 1.5 x bovenwaarde van normaal, Alkalish fosfatase > 2.0 × bovenwaarde van normaal)
6. Nierfunctiestoornis (GFR < 30 ml/min of dialyse)
7. zwangerschap
8. tijdens de trial gebruik van een sterke CYP1A2 remmer (fluvoxamine, enoxacine)

E.5 End points

E.5.1

Primary end point(s)

The primary objective is to investigate the safety and tolerability of pirfenidone in asbestosis patients as measured by weekly digital symptom and AE score

de primaire uitkomstmaat is beschrijvend: de veiligheid en verdraagzaamheid van pirfenidon in asbestose patienten, gemeten door wekelijkse rapportage van adverse events / AE's tijdens de behandeling

E.5.1.1

Timepoint(s) of evaluation of this end point

24 weeks after start of therapy

24 weken na start van therapie

E.5.2

Secondary end point(s)

Secondary objective is describing the effect of pirfenidone, as measured by daily home spirometry, in-hospital pulmonary function (spirometry and diffusion capacity), 6-minute walking test and patient reported outcomes as measured by King’s Brief Interstitial Lung disease Questionnaire (K-BILD) and Leicester Cough Questionnaire (LCQ).

secundaire uitkomstmaten beschrijven het effect van pirfenidon, gemeten dmv dagelijkse longfunctie(FVC) met een thuisspirometer, longfunctie (spirometrie en diffusie) in het ziekenhuis, 6 minuten- looptest en patient gerapporteerde uitkomstmaten dmv 2 vragenlijsten (King’s Brief Interstitial Lung disease Questionnaire (K-BILD) en Leicester Cough Questionnaire (LCQ).

E.5.2.1

Timepoint(s) of evaluation of this end point

24 weeks after start of therapy

24 weken na start van therapie

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

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)

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

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

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

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

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

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 OR specific criteria for end of trial in subject:

1.withdrawal from patient consent
2.consecutive treatment interruption > 28 days
3.patient unable to tolerate pirfenidone after titration period (≥ 3 times daily 534mg)
4.hepatic impairment ALT > 3x ULN and symtoms or hyperbilirubinaemia OR ALT >5xULN
5.renal impairment GFR <30 ml/min OR dialysis
6.any medical situation or adverse event classified as not acceptable by patient or investigator

LVLS OF specifieke criteria voor stoppen van de trial voor een patient:

1. terugtrekken van toestemming
2. onderbreking van behandeling gedurende > 28 dagen
3. intolerantie voor pirfenidon na titratie fase (≥ 3 dd 534mg)
4. leverenzymstoornis ALAT > 3x normaalwaarde en klachten of verhoogd bilirubine OF ALAT > 5x normaalwaarde
5. nierfunctiestoornis GFR < 30 ml/min OF dialyse
6. elke medische situatie of adverse event die wordt beoordeeld als niet acceptable door patient of onderzoeker

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

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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.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 trial, if the patient wants to continue the treatment with pirfenidone, up to 12 months of additional treatment is given. In this safety follow up period, trial results will be discussed with the Dutch 'Zorginstituut' to arrange for reimbursement of treatment with pirfenidone for asbestosis

Na het onderzoek, als de patient door wil gaan met de behandeling, zal additioneel 12 maanden behandeling worden gegeven. In deze safety follow up periode worden de resultaten van het onderzoek besproken met het Zorginstituut Nederland en gekeken worden of de behandeling kan worden vergoed voor patienten met asbestose

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-11-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-03-07

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

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