Clinical Trials Register

Summary
EudraCT Number:	2016-000068-40
Sponsor's Protocol Code Number:	FAIR-HF2
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:	2021-06-17
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

2016-000068-40

A.3

Full title of the trial

Intravenous iron in patients with systolic heart failure and iron deficiency to improve morbidity & mortality

Somministrazione di ferro per via endovenosa in pazienti con insufficienza cardiaca sistolica e carenza di ferro al fine di migliorare morbilità e mortalità

A.3.1

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

Study to investigate the improvement on morbitity and mortality and frequence of disease by intravenous iron therapy in patients with disturbance of heart function and iron deficiency

Studio per valutare il miglioramento della morbilità e mortalità e frequenza della malattia mediante terapia con ferro per via endovenosa in pazienti con disturbi della funzione cardiaca e carenza di ferro

A.3.2

Name or abbreviated title of the trial where available

Study to investigate the improvement on morbitity and mortality and frequence of disease by intraven

Studio per valutare il miglioramento della morbilità e mortalità e frequenza della malattia mediante

A.4.1

Sponsor's protocol code number

FAIR-HF2

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	UNIVERSITäTKLINIKUM HAMBURG-EPPENDORF
B.1.3.4	Country	Germany
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	Deutsches Zentum für Herz-Kreislauf-Forschung
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Vifor Pharma
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	University Medical Centre Hamburg-Eppendorf
B.5.2	Functional name of contact point	Mahir Karakas
B.5.3	Address:
B.5.3.1	Street Address	Martinistrasse 52
B.5.3.2	Town/ city	Hamburg
B.5.3.3	Post code	20246
B.5.3.4	Country	Germany
B.5.4	Telephone number	004940741057975
B.5.5	Fax number	004940741055619
B.5.6	E-mail	m.karakas@uke.de

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	Ferinject
D.2.1.1.2	Name of the Marketing Authorisation holder	Vifor France SA
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Ferinject 50 mg ferro/ml soluzione iniettabile/per infusione.
D.3.2	Product code	[Ferinject 50 mg ferro/ml soluzione iniettabile/pe
D.3.4	Pharmaceutical form	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	Carbossimaltosio Ferrico
D.3.9.2	Current sponsor code	carbossimaltosio ferrico
D.3.9.4	EV Substance Code	SUB66620
D.3.10	Strength
D.3.10.1	Concentration unit	1X 100 milligrams/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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

Systolic heart failure associated with iron deficiency

Insufficienza cardiaca sistolica associata a carenza di ferro

E.1.1.1

Medical condition in easily understood language

Reduces heart's pumping associated with iron deficiency

Diminuzione della funzione di pompaggio del cuore associata a carenza di ferro

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	LLT
E.1.2	Classification code	10074631
E.1.2	Term	Systolic heart failure
E.1.2	System Organ Class	100000004849

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the FAIR-HF2 trial is to show that treatment of patients with systolic heart failure and iron deficiency with i.v. iron (Ferric Carboxymaltose, FCM) versus placebo (i.v. NaCl) can reduce the rate of the combined endpoint of recurrent heart failure hospitalisations and cardiovascular death during at least 12 months follow-up.

L'obiettivo primario del trial FAIR-HF2 consiste nell'illustrare che il trattamento dei pazienti con insufficienza cardiaca sistolica e carenza di ferro con ferro per via endovenosa (Carbossimaltosio ferrico, FCM) rispetto al placebo (NaCl per via endovenosa) è in grado di ridurre il tasso dell'endpoint combinato di ospedalizzazioni ricorrenti per insufficienza cardiaca e morte cardiovascolare durante un follow-up di almeno 12 mesi.

E.2.2

Secondary objectives of the trial

Secondary objectives include the demonstration that in these patients treatment with FCM versus placebo can reduce the rate of recurrent cardiovascular hospitalisations, the rate of recurrent hospitalisations of any kind, and of all-cause mortality. An additional aim is to show the cost-effectiveness of the intervention.

Gli obiettivi secondari comprendono la dimostrazione che in questi pazienti il trattamento con FCM rispetto al placebo può ridurre il tasso delle ospedalizzazioni ricorrenti per CV, il tasso di ricoveri ricorrenti di
qualsiasi tipo e di mortalità per qualsiasi natura. Un ulteriore obiettivo è quello di illustrare il rapporto costo-efficacia dell'intervento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients with chronic HF (CHF) present for at least 12 months
2. Confirmed presence of ID (ferritin < 100 ng/mL or ferritin 100 - 299 ng/mL with TSAT < 20 %)
3. Serum haemoglobin of 9.5 to 14.0 g/dL
4. At time of screening considered re-stabilized and planned for discharge within next 24 h, or stable ambulatory with a HF hospitalisation in the past 6 months, or stable ambulatory with BNP > 100 pg/mL or NT-proBNP > 300 pg/mL or MR-proANP > 120 pmol/L
5. LVEF = 45 % (documented within the last 12 months prior to screening), NYHA class II or III
6. Written informed consent

1. Pazienti con HF cronica (CHF) presente per almeno 12 mesi
2. Presenza confermata di ID (ferritina < 100 ng/mL o ferritina 100 - 299 ng/mL con TSAT < 20%)
3. Emoglobina sierica pari a 9,5 - 14,0 g/dL
4. Soggetti che al momento dello screening siano considerati nuovamente stabilizzati e per i quali sia pianificata la dimissione entro le successive 24 h, oppure soggetti ambulatoriali con ospedalizzazione
per HF negli ultimi 6 mesi oppure soggetti ambulatoriali con BNP > 100
pg/mL o NT-proBNP > 300 pg/mL o MR-proANP > 120 pmol/L
5. LVEF = 45% (documentato negli ultimi 12 mesi precedenti allo screening), NYHA classe II o III
6. Consenso informato scritto

E.4

Principal exclusion criteria

1. Hypersensitivity to the active substance, to FCM or any of its excipients
2. Known serious hypersensitivity to other parenteral iron products
3. Anaemia not attributed to iron deficiency, e.g. other microcytic anaemia
4. Evidence of iron overload or disturbances in the utilisation of iron
5. History of severe asthma, eczema or other atopic allergy
6. History of immune or inflammatory conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis)
7. Acute or chronic infection
8. Presence of a deficiency for vitamin B12 and/or serum folate (if present, this needs to be corrected first)
9. Use of renal replacement therapy
10. Known allergy to FCM or its excipients
11. Treatment with an erythropoietin stimulating agent (ESA), any i.v. iron and/or a blood transfusion in the previous 6 weeks prior to randomization.

1. Ipersensibilità al principio attivo, all'FCM o ad uno qualsiasi degli eccipienti
2. Gravi ipersensibilità ad altri prodotti derivati del ferro per via parenterale
3. Anemia non attribuita a carenza di ferro, per es. altra anemia microcitica
4. Evidenza di sovraccarico da ferro o disturbi nell'utilizzo dello stesso
5. Anamnesi di asma severa, eczema o altra allergia atopica
6. Anamnesi di condizioni immuni o infiammatorie (ad es. lupus eritematoso sistemico, artrite reumatoide)
7. Infezione acuta o cronica
8. Presenza di carenza di vitamina B12 e/o folato sierico (se presente, ciò deve essere corretto per primo)
9. Ricorso a terapia renale sostitutiva
10. Allergia nota all'FCM o ai suoi eccipienti
11. Trattamento con agente stimolante l'eritropoietina (ESA), qualsiasi somministrazione di ferro per via endovenosa e/o trasfusione di sangue nelle 6 settimane precedenti la randomizzazione.

E.5 End points

E.5.1

Primary end point(s)

Combined rate of recurrent hospitalisations for heart failure and of CV death during follow-up

Tasso combinato di ospedalizzazioni ricorrenti per insufficienza cardiaca e morte CV durante il follow-up

E.5.1.1

Timepoint(s) of evaluation of this end point

At least after 12 month of follow up

Almeno dopo 12 mesi di follow-up

E.5.2

Secondary end point(s)

• Combined rate of recurrent CV hospitalisations and of CV death during follow-up
• Combined rate of recurrent hospitalisations for any reason and of CV death
• Rate of recurrent CV hospitalisations
• Rate of recurrent HF hospitalisations
• Rate of recurrent hospitalisations of any kind
• All-cause mortality
• CV mortality
• Changes in NYHA functional class, 6-minute walk-test, EQ-5D, and PGA of wellbeing during follow-up (from baseline to vari-ous time-points of follow-up)
• Changes in renal, cardiovascular, inflammatory and metabolic parameters from baseline to end of follow-up

• Tasso combinato di ospedalizzazioni CV ricorrenti e di morte CV durante il follow-up
• Tasso combinato di ospedalizzazioni ricorrenti per qualsiasi mo-tivo e di morte CV
• Tasso di ospedalizzazioni CV ricorrenti
• Tasso di ospedalizzazioni HF ricorrenti
• Tasso di ospedalizzazioni ricorrenti di qualsiasi tipo
• Mortalità per tutte le cause
• Mortalità CV
• Variazioni della classe funzionale NYHA, del test del cammino in 6 minuti, di EQ - 5D e della valutazione globale del benessere da parte del paziente (PGA) durante il follow-up (dal basale a vari time-point del follow-up)
• Variazioni dei parametri renali, cardiovascolari, infiammatori e metabolici dal basale alla fine del follow-up

E.5.2.1

Timepoint(s) of evaluation of this end point

At least after 12 month of follow up

Almeno dopo 12 mesi di follow-up

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

Serbia

Germany

Italy

Poland

Portugal

Slovenia

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:

600

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

600

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

Yes

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1100

F.4.2.2

In the whole clinical trial

1200

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

2018-02-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-04-18

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

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