Clinical Trials Register

Summary
EudraCT Number:	2019-002912-25
Sponsor's Protocol Code Number:	1VIT15043
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-09-26
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2019-002912-25

A.3

Full title of the trial

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Injectafer® (Ferric Carboxymaltose) as Treatment for Heart Failure with Iron Deficiency

A.3.1

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

Study to Investigate the Efficacy and Safety of Intravenous Injectafer® (Ferric Carboxymaltose) as Treatment for Heart Failure with Iron Deficiency

A.3.2

Name or abbreviated title of the trial where available

HEART-FID

A.4.1

Sponsor's protocol code number

1VIT15043

A.5.4

Other Identifiers

Name:

IND #

Number:

127910

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	American Regent, 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	American Regent, 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	American Regent Inc
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	800 Adams Avenue, Suite 200
B.5.3.2	Town/ city	Norristown
B.5.3.3	Post code	PA 19403
B.5.3.4	Country	United States
B.5.4	Telephone number	+1 610 650 4200
B.5.5	Fax number	+1 610 650 7781

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	Injectafer®
D.2.1.1.2	Name of the Marketing Authorisation holder	American Regent Inc.,
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Injectafer®
D.3.4	Pharmaceutical form	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.3.8	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	Injection
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

Heart Failure with Iron Deficiency

E.1.1.1

Medical condition in easily understood language

Heart Failure 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	10022974
E.1.2	Term	Iron deficiency anemia
E.1.2	System Organ Class	100000004851

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	10019279
E.1.2	Term	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 this study is to determine the efficacy and
safety of iron therapy using intravenous (IV) ferric carboxymaltose
(FCM), relative to placebo, in the treatment of participants in heart
failure with a reduced ejection fraction and with iron deficiency.

E.2.2

Secondary objectives of the trial

To evaluate the effect of IV FCM, relative to placebo, on the functional capacity of patients in heart failure with reduced ejection fraction and with iron deficiency.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

A sub-study to characterize serum phosphorus levels over time with intravenous ferric carboxymaltose (FCM) vs. placebo as treatment for heart failure with iron deficiency.
Appendix 1 to Protocol No.: 1VIT15043 Version 3 Date: Final 11 January 2021.
The objective of this sub-study is to characterize serum phosphorus levels over time in participants with heart failure with iron deficiency after dosing with FCM versus placebo.

E.3

Principal inclusion criteria

1. Adult (≥18 years of age) able to provide signed, written informed consent.
2. Stable heart failure (NYHA II-IV) on maximally-tolerated
background therapy (as determined by the site Principle
Investigator) for at least 2 weeks prior to randomization.
3. Able and willing to perform a 6MWT at the time of
randomization.
4. Reduced left ventricular ejection fraction. Assessment must be performed at least 12 weeks after major cardiac surgical
intervention including coronary artery bypass graft (CABG),valvular repair/replacement, or cardiac resynchronization therapy
(CRT) device implantation.
a. Left ventricular ejection fraction ≤40% obtained during
the screening visit OR either of the following
i. Historical value of ejection fraction ≤40% within 24 months of screening visit
ii. Historical value of ejection fraction ≤30% within 36 months of screening visit
5. Hemoglobin >9.0 g/dL and <13.5 g/dL (females) or <15.0 g/dL
(males) within 28 days of randomization.
6. Serum ferritin <100 ng/mL or 100 to 300 ng/mL with TSAT
<20%. Patients with screening ferritin <15 ng/mL must have
documentation of an appropriate evaluation, as determined by the
Principle Investigator, within 3 months of screening and prior to
randomization.
7. Either documented hospitalization for heart failure within 12
months of enrollment or elevated N-terminal-pro-brain natriuretic
peptide (NT-proBNP) within 90 days of randomization:
a. For patients in normal sinus rhythm: N-terminal-pro-brain
natriuretic peptide (NT-proBNP) >600 pg/mL (or BNP
>200 pg/mL)
b. For patients in atrial fibrillation: NT-proBNP >1000
pg/mL (or BNP >400 pg/mL

E.4

Principal exclusion criteria

1. Known hypersensitivity reaction to any component of FCM.
2. History of acquired iron overload, or the recent receipt (within 3 months) of erythropoietin stimulating agent, IV iron therapy, or blood transfusion.
3. Acute myocardial infarction, acute coronary syndrome, transient ischemic attack, or stroke within 30 days of enrollment.
4. Uncorrected severe aortic stenosis, severe valvular regurgitation (except mitral regurgitation due to left ventricular dilatation without planned intervention), or left ventricular outflow obstruction requiring intervention.
5. Current atrial fibrillation or atrial flutter with a mean ventricular response rate >100 per minute (at rest).
6. Current or planned mechanical circulatory support or heart transplantation.
7. Hemodialysis or peritoneal dialysis (current or planned within the next 6 months).
8. Documented liver disease, or active hepatitis (i.e. alanine transaminase or aspartate transaminase >3 times the upper limit of normal range).
9. Current or recent (within 3 years) malignancy with exception of basal cell carcinoma or squamous cell carcinoma of the skin, or cervical intraepithelial neoplasia.
10. Active gastrointestinal bleeding.
11. Female participant of child-bearing potential who is pregnant, lactating, or not willing to use adequate contraceptive precautions during the study and for up to 5 days after the last scheduled dose of study medication.
12. Inability to return for follow up visits within the necessary windows
13. Concurrently in a study with investigational product.
14. Current COVID-19 infection.

E.5 End points

E.5.1

Primary end point(s)

Hierarchical composite of 1) death, 2) hospitalization for heart
failure (defined in section 10.2), or 3) change in 6MWT. (Death and hospitalizations for heart failure will be evaluated at one year,
Change in 6MWT will be evaluated at 6 months) and tested using the nonparametric Wilcoxon-type test.

E.5.1.1

Timepoint(s) of evaluation of this end point

as above

E.5.2

Secondary end point(s)

1. Time to first event of the composite of cardiovascular death or heart failure hospitalization. The composite endpoint will be
composed of adjudicated occurrence of one of the following:
a. Cardiovascular Death
i. Death due to Heart Failure
ii. Death due to Acute Myocardial Infarction
iii. Sudden Cardiac Death
iv. Death due to Stroke
v. Death due to other Cardiovascular Causes
b. Hospitalization for Worsening Heart Failure
2. Mean change in 6MWT from baseline to 12 months
3. Time to first event of the composite of cardiovascular death or intervention for worsening heart failure (hospitalization or urgent heart failure visits)
4. Time to first event of the composite of cardiovascular death and cardiovascular hospitalizations
5. Time to cardiovascular death

Additional events to be adjudicated for analysis of the secondary endpoints include:
a) Non-cardiovascular death
b) Hospitalization for myocardial infarction
c) Hospitalization for stroke
d) Other cardiovascular hospitalizations
e) Urgent heart failure visits

E.5.2.1

Timepoint(s) of evaluation of this end point

as above

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

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)

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

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

Australia

Canada

New Zealand

United States

Georgia

Ukraine

Poland

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

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:

1508

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

1508

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

180

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1508

F.4.2.2

In the whole clinical trial

3014

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

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

2019-11-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-10-24

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-02-02

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IMP with orphan designation in the indication
Orphan Designation Number:
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