Clinical Trials Register

Summary
EudraCT Number:	2016-000068-40
Sponsor's Protocol Code Number:	FAIR-HF2
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-09-12
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

Hungary - National Institute of Pharmacy

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

Intravénás vas alkalmazása szisztolés szívelégtelenségben szenvedő, vashiányos betegeknél a morbiditás és a mortalitás javítása érdekében

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

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	University Medical Centre 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.3.4	Pharmaceutical form	Solution for injection/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	FERRIC CARBOXYMALTOSE
D.3.9.1	CAS number	9007-72-1
D.3.9.4	EV Substance Code	SUB66620
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	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	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	Solution for injection/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

E.1.1.1

Medical condition in easily understood language

Reduces heart's pumping associated with iron deficiency

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.

A FAIR-HF2 vizsgálat elsődleges célja annak kimutatása, hogy szisztolés szívelégtelenségben szenvedő, vashiányos betegek iv. vassal (vas(III)-
karboximaltózzal, VKM) való kezelése, placebóval (iv. NaCl) összehasonlítva, csökkenti a szívelégtelenség miatti ismételt kórházi felvételeket és a
kardiovaszkuláris halált magában foglaló kombinált végpont gyakoriságát a legalább 12 hónapos utánkövetés során.

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.

A másodlagos célok között annak kimutatása szerepel, hogy ezeknél a betegeknél a VKM-mel való kezelés, a placebóhoz képest, csökkenti a
kardiovaszkuláris ok miatti ismételt kórházi felvételek gyakoriságát, a bármilyen okból bekövetkező ismételt kórházi felvételek gyakoriságát, valamint a
bármilyen okú mortalitást. További cél az intervenció költséghatékonyságának kimutatása.

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. A betegnél legalább 12 hónapja krónikus szívelégtelenség áll fenn.
2. Vashiány megerősített fennállása (ferritin < 100 ng/ml vagy ferritin
100–299 ng/ml és TSAT < 20%)
3. Szérum hemoglobin 9,5–14,0 g/dl
4. A szűrés időpontjában a beteg újra stabil, és 24 órán belül
elbocsátását tervezik, vagy stabil járóbeteg az elmúlt 6 hónapban
szívelégtelenség miatti kórházi felvétellel, vagy stabil járóbeteg, akinél
a BNP > 100 pg/ml vagy NT-proBNP > 300 pg/ml vagy MR-proANP
> 120 pmol/l
5. LVEF ≤ 45% (dokumentálva a szűrést megelőző 12 hónapban),
NYHA II-es vagy III-as stádium
6. Tájékoztatáson alapuló írásos beleegyezés

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. A hatóanyaggal, a VKM-mel, vagy bármely segédanyagával szembeni
túlérzékenység
2. Ismert komoly túlérzékenység más parenterális vaskészítményekkel
szemben
3. Nem vashiány miatti vérszegénység, például más microcytaer
anaemia
4. Vastúlterhelés vagy vasfelhasználási zavarok bizonyítéka
5. Súlyos asztma, ekcéma vagy más atópiás allergia az anamnézisben
6. Immunrendszeri vagy gyulladásos kórállapotok az anamnézisben
(például szisztémás lupus erythematosus, rheumatoid arthritis)
7. Akut vagy krónikus fertőzés
8. B12-vitamin és/vagy folsav hiánya (ha fennáll, akkor először korrigálni
kell)
9. Vesepótló kezelés alkalmazása
10. Ismert allergia a VKM-re vagy bármely összetevőjére
11. Eritropoezis-serkentő szerrel (ESA) végzett kezelés, bármilyen
iv. vas és/vagy vérátömlesztés a randomizálást megelőző 6 hétben

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

Szívelégtelenség miatti ismételt kórházi felvételek és kardiovaszkuláris halál kombinált gyakorisága az utánkövetés során

E.5.1.1

Timepoint(s) of evaluation of this end point

At least after 12 month of follow up

Legalább 12 hónapos utánkövetés után.

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

· Szívelégtelenség miatti ismételt kórházi felvételek és kardiovaszkuláris halál kombinált gyakorisága az utánkövetés során
· Bármilyen ok miatti ismételt kórházi felvételek és kardiovaszkuláris halál kombinált gyakorisága
· Kardiovaszkuláris ok miatti ismételt kórházi felvételek gyakorisága
· Szívelégtelenség miatti ismételt kórházi felvételek gyakorisága
· Bármilyen ok miatti ismételt kórházi felvételek gyakorisága
· Bármilyen okú mortalitás
· Kardiovaszkuláris mortalitás
· A NYHA funkcionális stádium, a 6 perces járásvizsgálat, az EQ-5D és a jóllétre vonatkozó PGA változása az utánkövetés során (a kiindulástól az utánkövetés különböző időpontjáiig)
· A renális, kardiovaszkuláris, gyulladásos és metabolikus paraméterek változása a kiindulástól az utánkövetés végéig

E.5.2.1

Timepoint(s) of evaluation of this end point

At least after 12 month of follow up

Legalább 12 hónapos utánkövetés után.

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

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

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

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

LPLV

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

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

700

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

Nincs

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

2016-12-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-11-23

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

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