Clinical Trials Register

Summary
EudraCT Number:	2017-002667-17
Sponsor's Protocol Code Number:	CVAY736X2207
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-02-13
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2017-002667-17

A.3

Full title of the trial

A subject-, investigator-, and sponsor-blinded, randomized, placebo-controlled, multicenter study to investigate efficacy, safety, and tolerability of VAY736 in patients with idiopathic pulmonary fibrosis

Studio multicentrico, in cieco per il soggetto, lo sperimentatore e lo sponsor,
randomizzato, controllato con placebo volto a valutare l’efficacia, la sicurezza e la tollerabilità di VAY736 in pazienti con fibrosi
polmonare idiopatica

A.3.1

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

Study of pharmacodynamics, pharmacokinetics, safety and tolerability of VAY736 in patients with idiopathic pulmonary fibrosis

Studio di farmacodinamica,
farmacocinetica, sicurezza e tollerabilità di VAY736 in pazienti con fibrosi polmonare idiopatica

A.3.2

Name or abbreviated title of the trial where available

Study of pharmacodynamics,pharmacokinetics, safety and tolerability of VAY736 in patients with idiop

Studio di farmacodinamica, farmacocinetica, sicurezza e tollerabilità di VAY736 in pazienti con fibr

A.4.1

Sponsor's protocol code number

CVAY736X2207

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03287414

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	Novartis Pharma AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Ireland Limited
B.5.2	Functional name of contact point	Medical Information Department
B.5.3	Address:
B.5.3.1	Street Address	Beech House , Beech Hill Office Campus - Clonskeagh
B.5.3.2	Town/ city	Clonskeagh
B.5.3.3	Post code	Dublin 4
B.5.3.4	Country	Ireland
B.5.4	Telephone number	+353 12601255
B.5.5	Fax number	+353 12601263
B.5.6	E-mail	medinfo.dublin@novartis.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.3.2	Product code	VAY736
D.3.4	Pharmaceutical form	Powder for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	not established
D.3.9.3	Other descriptive name	VAY736
D.3.9.4	EV Substance Code	SUB31641
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	150
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)	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	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/infusion
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Idiopathic pulmonary fibrosis

fibrosi polmonare idiopatica

E.1.1.1

Medical condition in easily understood language

Scar tissue in the lung that interferes with the ability to breathe

Tessuto cicatriziale nel polmone che interferisce con la
capacità di respirare

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	10021240
E.1.2	Term	Idiopathic pulmonary fibrosis
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 the efficacy of VAY736 in patients with idiopathic pulmonary fibrosis

Valutare l’efficacia di VAY736 in pazienti con FPI

E.2.2

Secondary objectives of the trial

Impact of VAY736 on survival and disease progression.

Other protocol-defined secondary objectives may apply

Valutare l’impatto di VAY736 sulla sicurezza e la progressione della malattia.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent must be obtained before any assessment is performed.
2. Male and female subjects 40 to 80 years of age inclusive
3. A diagnosis of definite or probable IPF within 5 years of the screening visit, as defined by the ATS/ERS/JRS/ALAT Diagnostic Guidelines (Raghu et al 2011)
4. Seropositive at screening for at least one of the following auto-antibodies: RF, ANA, anti-dsDNA, anti-CCP, Scl-70, SSA (anti-Ro), SSB (anti-La), anti-RNP, anti-Smith, Jo-1, PL-7, PL-12, EJ, OJ, SRP, Ku, Mi-2, anti-PM/Scl;
OR
Presence of hilar/mediastinal adenopathy (>1cm in short-axis diameter), identified by screening HRCT scan of the chest
5. FVC 50-90% predicted (inclusive)
6. DLCO, corrected for hemoglobin, 30-79% predicted (inclusive)
7. FEV1/FVC >70%
8. Unlikely to die from cause other than IPF within the next 3 years, in the opinion of the investigator
9. Unlikely to undergo lung transplantation during this trial
10. Able to communicate well with the investigator, to understand and comply with the requirements of the study.

Other protocol-defined inclusion/exclusion criteria may apply

•Il consenso informato scritto deve essere ottenuto prima che sia eseguita qualsiasi valutazione.
•Soggetti di sesso maschile e femminile di età compresa tra 40 e 80 anni compresi
•Diagnosi di FPI definita o probabile entro 5 anni dalla visita di screening, secondo quanto stabilito dalle linee guida diagnostiche
ATS/ERS/JRS/ALAT
•Sieropositività allo screening per almeno uno dei seguenti autoanticorpi: RF, ANA, anti-dsDNA, anti-CCP, Scl-70, SSA (anti-Ro),
SSB (anti-La), anti-RNP, anti-Smith, Jo-1, PL-7, PL-12, EJ, OJ, SRP, Ku, Mi-2, anti-PM/Scl; OPPURE Presenza di adenopatia
ilare/mediastinica (>1 cm nel diametro dell’asse minore), identificata mediante scansione HRCT del torace eseguita allo screening
•CVF 50-90% del valore previsto (compreso)
•Diffusione alveolo-capillare del monossido di carbonio (DLCO), corretta per l’emoglobina, al 30-79% del valore previsto
(compreso)
•Volume espiratorio massimo in 1 secondo (VES1)/(CVF) >70%
•Bassa probabilità di morire per una causa diversa da FPI nei 3 anni successivi, secondo il parere dello sperimentatore
•Bassa probabilità di doversi sottoporre a un trapianto di polmone durante questa sperimentazione
• In grado di comunicare bene con l'investigatore, per capire e rispettare i requisiti dello studio.
Possono essere applicati altri criteri di inclusione / esclusione definiti dal protocollo

E.4

Principal exclusion criteria

1. Emphysema > fibrosis on screening HRCT (must be confirmed by central reader)
2. Active viral, bacterial or other infections requiring systemic treatment at the time of screening or enrollment, or history of recurrent clinically significant infection or of bacterial infections with encapsulated organisms
3. History of major organ, hematopoietic stem cell or bone marrow transplant
4. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes (e.g., mAb of IgG1 class) or to any of the constituents of the study drug (sucrose, L-Arginine hydrochloride, L-histidine, polysorbate 80, hydrochloric acid)
5. Receipt of live/attenuated vaccine within a 2 month period before baseline
6. History of primary or secondary immunodeficiency, including a positive Human Immunodeficiency Virus (HIV) (Enzyme-linked Immunosorbent Assay (ELISA) and Western blot) test result
7. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin, in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
8. Any one of the following screening values of complete blood count laboratory values: Hemoglobin levels below 8.0 g/dL; Total leukocyte count less than 2,000/μL; Platelets <100.0 x 109/L; Absolute neutrophil count (ANC) <1.5 x 109/L
9. Any surgical, medical (e.g., uncontrolled hypertension, heart failure or diabetes), psychiatric or additional physical condition that the Investigator feels may jeopardize the patient in case of participation in this study
10. Positive hepatitis B surface antigen (HBsAg) with concurrent negative hepatitis B surface antibody (anti-HBs); or positive total hepatitis B core antibody (anti-HBc) with concurrent negative anti-HBs; or positive hepatitis C antibody (anti-HCV); i.e., any acute or chronic infection with hepatitis B or hepatitis C
11. Evidence of active or latent tuberculosis (TB) infection, as determined by Quantiferon test (after anti-TB treatment, patients with history of or latent TB may become eligible according to national guidelines)

Other protocol-defined inclusion/exclusion criteria may apply

•Enfisema > fibrosi alla scansione HRCT eseguita allo screening (deve essere confermata mediante lettura centrale)
•Infezioni virali attive, batteriche o di altro tipo che richiedono un trattamento sistemico al momento dello screening o
dell'arruolamento o anamnesi di recidiva di infezione clinicamente significativa o di infezioni batteriche con organismi incapsulati
•Anamnesi di trapianto di uno dei principali organi, cellule staminali ematopoietiche o midollo osseo
•Anamnesi di ipersensibilità a uno qualsiasi dei farmaci in studio o ai farmaci di classi chimiche simili (ad esempio, mAb di classe
IgG1) o a uno qualsiasi dei componenti del farmaco in studio (saccarosio, L-Arginina cloridrato, L-istidina, polisorbato 80, acido
cloridrico)
•Ha ricevuto un vaccino vivo / attenuato entro un periodo di 2 mesi prima del basale
•Anamnesi di immunodeficienza primaria o secondaria, incluso un risultato del test positivo del virus dell'immunodeficienza umana
(HIV) (saggio di immunoassorbimento enzimatico collegato (ELISA) e Western blot)
•Anamnesi di malignità di qualsiasi sistema di organi (diverso dal carcinoma a cellule basali localizzate della cute, carcinoma
cervicale in situ), trattati o non trattati, negli ultimi 5 anni, indipendentemente dal fatto che vi sia evidenza di recidiva locale o
metastasi
•Uno qualsiasi dei seguenti valori di screening dei valori di laboratorio con emocromo completo: livelli di emoglobina inferiori a 8,0
g / dl; Conta leucocitaria totale inferiore a 2.000 / μL; Piastrine <100,0 x 109 / L; Conteggio assoluto dei neutrofili (ANC) <1,5 x 109
/ L
•Qualsiasi intervento chirurgico, medico (per esempio ipertensione non controllata, insufficienza cardiaca o diabete), psichiatrico o
condizione fisica aggiuntiva che l'Investigatore ritiene possa mettere a repentaglio il paziente in caso di partecipazione a questo
studio
•HBsAg positivo con anti-HBs negativo; o anti-HBc positivo con anti-HBs concomitante negativo; o anticorpo anti-epatite C positivo
(anti-HCV); cioè qualsiasi infezione acuta o cronica con epatite B o epatite C
•Evidenza di tubercolosi (TB) attiva o latente, determinata dal test Quantiferon (dopo il trattamento anti-TB, i pazienti con storia di
tubercolosi latente o latente possono diventare idonei secondo le linee guida nazionali)
Possono essere applicati altri criteri di inclusione / esclusione definiti dal protocollo

E.5 End points

E.5.1

Primary end point(s)

Change from baseline to end of treatment epoch (48 weeks of treatment) in Forced Vital Capacity (FVC).

variazione dal basale a fine trattamento (48 settimane di trattamento) nella capacità vitale forzata (CVF)

E.5.1.1

Timepoint(s) of evaluation of this end point

end of treatment epoch (48 weeks of treatment)

fine trattamento (48 settimane di trattamento)

E.5.2

Secondary end point(s)

All-Cause mortality; Progression-free survival (PFS); Disease progression; Composite Endpoint; Change from baseline to end of treatment epoch (Week 48) in Diffusing Capacity of the Lungs (DLCO); Change from baseline to the end of treatment epoch (Week 48) in 6-minute walk test and in distance-saturation product; Change from baseline to the end of treatment epoch (Week 48) in resting oxygen saturation (on room air); Immunogenicity of VAY736; To assess the pharmacokinetics Cmin,ss of VAY736 after multiple s.c. doses; Idiopathic Pulmonary Fibrosis (IPF) -related Mortality; Change from baseline to end of treatment epoch (Week 48) in Total Lung Capacity (TLC)
Other protocol defined endpoints may apply

Mortalità per tutte le cause; Sopravvivenza libera da progressione (PFS); progressione della
Malattia; Endpoint composito; Cambiamento dal basale alla fine del trattamento (Settimana 48) nella Capacità di diffusione dei
polmoni (DLCO);
cambiamento dal basale alla fine del trattamento (settimana 48) nel test della camminata di 6 minuti e nel prodotto di saturazione
della distanza; Cambiamento dal basele alla fine del trattamento (settimana 48) nella saturazione dell'ossigeno a riposo (sull'aria
della stanza); Immunogenicità di VAY736; Per valutare la farmacocinetica Cmin, ss di VAY736 dopo dosi multiple s.c.;
Mortalità da Fibrosi Polmonare Idiopatica (IPF); Cambiamento dal basale alla fine del trattamento (settimana 48) nella capacità polmonare totale (TLC)
Possono essere applicati altri endpoint definiti dal protocollo

E.5.2.1

Timepoint(s) of evaluation of this end point

across the 48 weeks of treatment and at the end of study

nelle 48 settimane di trattamento e alla fine dello studio

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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

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

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

Canada

France

Germany

Ireland

Italy

United Kingdom

United States

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

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.4.2.2

In the whole clinical trial

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

Nessuno

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

2018-09-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-09-17

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-02-13

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