Clinical Trials Register

Summary
EudraCT Number:	2019-001458-24
Sponsor's Protocol Code Number:	ALN-TTR02-011
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-01-22
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2019-001458-24

A.3

Full title of the trial

APOLLO-B: A Phase 3, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Patisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy (ATTR Amyloidosis with Cardiomyopathy)

APOLLO-B: Studio di fase 3, randomizzato, in doppio cieco, controllato con placebo, multicentrico per valutare l'efficacia e la sicurezza di Patisiran in pazienti con amiloidosi da transtiretina con cardiomiopatia (amiloidosi ATTR con cardiomiopatia)

A.3.1

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

A study to Evaluate Patisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy

Studio per la valutazione di patisiran in pazienti affetti da amiloidosi da transtiretina con cardiomiopatia

A.3.2

Name or abbreviated title of the trial where available

A study to Evaluate Patisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy

Studio per la valutazione di patisiran in pazienti affetti da amiloidosi da transtiretina con cardio

A.4.1

Sponsor's protocol code number

ALN-TTR02-011

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	ALNYLAM PHARMACEUTICALS, INC.
B.1.3.4	Country	United States
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	Alnylam Pharmaceuticals, Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Alnylam Pharmaceuticals, Inc
B.5.2	Functional name of contact point	Clinical Trials Information Line
B.5.3	Address:
B.5.3.1	Street Address	300 Third Street
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	02142
B.5.3.4	Country	United States
B.5.4	Telephone number	0018772569526
B.5.5	Fax number	000000
B.5.6	E-mail	clinicaltrials@alnylam.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	Yes
D.2.1.1.1	Trade name	Onpattro
D.2.1.1.2	Name of the Marketing Authorisation holder	Alnylam Netherlands B.V.
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/3/11/857
D.3 Description of the IMP
D.3.1	Product name	Patisiran
D.3.2	Product code	[ALN-TTR02]
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PATISIRAN
D.3.9.1	CAS number	1386913-72-9
D.3.9.2	Current sponsor code	ALN-TTR02
D.3.9.4	EV Substance Code	SUB189946
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Yes
D.2.1.1.1	Trade name	BISOPROLOLO DOC - 5 MG COMPRESSE 56 COMPRESSE IN BLISTER PVC/PVDC/AL
D.2.1.1.2	Name of the Marketing Authorisation holder	DOC GENERICI SRL
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Decadron 4 MG/1 ML Soluzione iniettabile
D.3.2	Product code	[Decadron 4 MG/1 ML Soluzione iniettabile]
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	Decadron
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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: 3
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	Tachipirina
D.2.1.1.2	Name of the Marketing Authorisation holder	ANGELINI SPA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Tachipirina 500 mg compresse
D.3.2	Product code	[Tachipirina 500 mg compresse]
D.3.4	Pharmaceutical form	Tablet
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.3.9.2	Current sponsor code	paracetamolo
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	500
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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: 4
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	Trimeton
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer SPA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Trimeton
D.3.2	Product code	[Trimeton]
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	clorfenamina maleato
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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: 5
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	Famotidina EG
D.2.1.1.2	Name of the Marketing Authorisation holder	EG S.p.A
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Famotidina EG
D.3.2	Product code	[Famotidina EG]
D.3.4	Pharmaceutical form	Film-coated tablet
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.3.9.2	Current sponsor code	Famotidina
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	20
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Transthyretin Amyloidosis with Cardiomyopathy (ATTR Amyloidosis with Cardiomyopathy)

Amiloidosi da transtiretina con cardiomiopatia (amiloidosi ATTR con cardiomiopatia)

E.1.1.1

Medical condition in easily understood language

Transthyretin Amyloidosis with Cardiomyopathy (ATTR Amyloidosis with Cardiomyopathy)

Amiloidosi da transtiretina con cardiomiopatia (amiloidosi ATTR con cardiomiopatia)

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

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	10007509
E.1.2	Term	Cardiac amyloidosis
E.1.2	System Organ Class	10007541 - Cardiac disorders

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 evaluate the efficacy of patisiran compared with placebo treatment on functional capacity (6-minute walk test [6-MWT]) in patients with ATTR amyloidosis with cardiomyopathy

Valutare l'efficacia di patisiran rispetto al trattamento con placebo sulla capacità funzionale (test del cammino in 6 minuti [6-MWT]) in pazienti affetti da amiloidosi ATTR con cardiomiopatia

E.2.2

Secondary objectives of the trial

To evaluate the efficacy of patisiran compared with placebo treatment on:
- Health status and health-related quality of life
- Patient mortality and hospitalizations

Valutare l’efficacia di patisiran rispetto al trattamento con placebo su:
- Stato di salute e qualità della vita correlata allo stato di salute
- Mortalità e ospedalizzazioni dei pazienti

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age 18 (or age of legal consent, whichever is older) to 85 years, inclusive.
2. Documented diagnosis of ATTR amyloidosis with cardiomyopathy, classified as either hATTR amyloidosis with cardiomyopathy or wtATTR amyloidosis with cardiomyopathy:
Hereditary ATTR amyloidosis with cardiomyopathy diagnosed based on
meeting all of the following criteria:
a. TTR pathogenic mutation consistent with hATTR.
b. Evidence of cardiac involvement by echocardiography with an enddiastolic interventricular septal wall thickness >12 mm (based on central echocardiogram reading at screening).
c. Amyloid deposits in cardiac or noncardiac tissue (eg, fat pad aspirate, salivary gland, median nerve connective sheath) confirmed by Congo Red (or equivalent) staining OR technetium (99mTc) scintigraphy (99mTc-3,3-diphosphono-1,2 propanodicarboxylic acid [DPD-Tc] or 99mTc-pyrophosphate [PYP-Tc]) with Grade 2 or 3 cardiac uptake, if monoclonal
gammopathy of undetermined significance (MGUS) has been excluded.
d. If MGUS, confirm TTR protein in tissue with immunohistochemistry (IHC) or mass spectrometry.
Wild-type ATTR amyloidosis with cardiomyopathy diagnosed based on meeting all of the following criteria:
a. Absence of pathogenic TTR mutation.
b. Evidence of cardiac involvement by echocardiography with an enddiastolic interventricular septal wall thickness >12mm (based on central echocardiogram reading at screening).
c. Amyloid deposits in cardiac tissue with TTR precursor identification by IHC, mass spectrometry, OR technetium (99mTc) scintigraphy (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid [DPD-Tc] or 99mTc-pyrophosphate [PYP-Tc]) with Grade 2 or 3 cardiac uptake, if MGUS has been excluded.
d. If MGUS, confirm TTR protein in cardiac tissue with IHC or mass spectrometry
FOR THE COMPLETE LIST, REFER TO THE PROTOCOL

1. Età compresa tra i 18 (o l'età minima necessaria per fornire il consenso legale, a seconda di quale sia la più elevata) e gli 85 anni inclusi.
2. Diagnosi documentata di amiloidosi ATTR con cardiomiopatia, classificata come amiloidosi hATTR con cardiomiopatia o amiloidosi wtATTR con cardiomiopatia:
Amiloidosi ATTR ereditaria con cardiomiopatia diagnosticata sulla base del soddisfacimento di tutti i seguenti criteri:
a. Mutazione patogena della TTR coerente con hATTR.
b. Evidenza di coinvolgimento cardiaco ottenuta mediante ecocardiogramma con spessore telediastolico della parete del setto interventricolare >12 mm (basato sulla lettura dell’ecocardiogramma eseguito centralmente allo screening).
c. Depositi di amiloide nel tessuto cardiaco o non cardiaco (ad es. aspirato del tessuto adiposo, ghiandola salivare, guaina connettiva del nervo mediano) confermati mediante colorazione Rosso Congo (o equivalente) O scintigrafia con tecnezio (99mTc) (99mTc-3,3-difosfono-1,2-acido propanodicarbossilico [DPD-Tc] o 99mTc-pirofosfato [PYP-Tc]) con assorbimento cardiaco di grado 2 o 3, in caso di esclusione di gammopatia monoclonale di significato incerto (MGUS).
d. In caso di MGUS, conferma della presenza di proteina TTR nei tessuti mediante immunoistochimica (IHC) o spettrometria di massa.
Amiloidosi ATTR wild-type con cardiomiopatia diagnosticata sulla base del soddisfacimento di tutti i seguenti criteri:
a. Assenza di mutazioni patogene della TTR.
b. Evidenza di coinvolgimento cardiaco ottenuta mediante ecocardiogramma con spessore telediastolico della parete del setto interventricolare >12 mm (basato sulla lettura dell’ecocardiogramma eseguito centralmente allo screening).
c. Depositi di amiloide nel tessuto cardiaco con identificazione del precursore della TTR mediante IHC, spettrometria di massa O scintigrafia con tecnezio (99mTc) (99mTc-3,3-difosfono-1,2-acido propanodicarbossilico [DPD-Tc] o 99mTc-pirofosfato [PYP-Tc]) con assorbimento cardiaco di grado 2 o 3, in caso di esclusione di MGUS.
d. In caso di MGUS, conferma della presenza di proteina TTR nel tessuto cardiaco mediante IHC o spettrometria di massa
PER L'ELENCO COMPLETO RIFERIRSI AL PROTOCOLLO

E.4

Principal exclusion criteria

1. Has known primary amyloidosis (AL) or leptomeningeal amyloidosis.
2. NYHA Class III AND ATTR amyloidosis disease Stage 3 (defined as both NT-proBNP >3000 ng/L and estimated glomerular filtration rate [eGFR] <45 ml/min/1.73 m2).[Gillmore 2018]
3. NYHA Class IV at the Screening visit.
4. Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV (requires cane or stick to walk, or is wheelchair bound) at the Screening visit.
FOR THE COMPLETE LIST, REFER TO THE PROTOCOL

1. Soffre di amiloidosi primaria (AL) o amiloidosi leptomeningea nota.
2. Presenta una classe III secondo la NYHA E malattia amiloide ATTR allo stadio 3 (definito da NT proBNP >3000 ng/l e velocità di filtrazione glomerulare stimata [eGFR] <45 ml/min/1,73 m2) [Gillmore 2018]
3. Presenta una classe IV secondo la NYHA alla Visita di screening.
4. Ha una disabilità da polineuropatia (PND) con punteggio IIIa, IIIb o IV (necessita di assistenza alla deambulazione con bastone o stampella o è costretto sulla sedia a rotelle) alla Visita di Screening.
PER L'ELENCO COMPLETO RIFERIRSI AL PROTOCOLLO

E.5 End points

E.5.1

Primary end point(s)

Change from baseline at Month 12 in 6-MWT

Variazione rispetto alla baseline al Mese 12 del test 6-MWT

E.5.1.1

Timepoint(s) of evaluation of this end point

Month 12

mese 12

E.5.2

Secondary end point(s)

- Change from baseline at Month 12 in Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score
- Composite endpoint of all-cause mortality, frequency of cardiovascular (CV)-related hospitalizations and change from baseline in 6-MWT over the 12-month double-blind period
- Composite endpoint of all-cause mortality and frequency of all-cause hospitalizations over the 12-month double-blind period

- Variazione rispetto alla baseline al Mese 12 del punteggio del Questionario sulla cardiomiopatia Kansas City-Sintesi complessiva (KCCQ-OS)
- Indice composito di mortalità per tutte le cause, frequenza delle ospedalizzazioni per eventi cardiovascolari (CV) e variazione rispetto alla baseline del test 6-MWT nel corso del periodo in doppio cieco di 12 mesi
- Indice composito di mortalità per tutte le cause e frequenza delle ospedalizzazioni per tutte le cause nel corso del periodo in doppio cieco di 12 mesi al Mese

E.5.2.1

Timepoint(s) of evaluation of this end point

Month 12 (Weeks 52-53); this assessment will also be performed at Month 6 (Weeks 25-26) and Month 9 (Weeks 37-38

Al mese 12 (Settimane 52-53); tale valutazione verrà eseguita anche al Mese 6 (Settimane 25-26) e al Mese 9 (Settimane 37-38)

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

Yes

E.6.7

Pharmacodynamic

Yes

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

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

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

Information not present in EudraCT

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

Australia

Brazil

Colombia

Hong Kong

Japan

Korea, Republic of

Mexico

Taiwan

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

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:

210

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

175

F.4.2.2

In the whole clinical trial

300

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

2019-11-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-08-28

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

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Orphan Designation Number:
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