Clinical Trials Register

Summary
EudraCT Number:	2017-000776-29
Sponsor's Protocol Code Number:	P-Monofer-PREG-01
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-02-22
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

Denmark - DHMA

A.2

EudraCT number

2017-000776-29

A.3

Full title of the trial

Intravenous iron isomaltoside versus oral iron supplementation for treatment of iron deficiency in pregnancy:
a randomised, comparative, open-label trial

A.3.1

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

Treatment of pregnant women with iron deficiency

A.3.2

Name or abbreviated title of the trial where available

P-Monofer-PREG-01

A.4.1

Sponsor's protocol code number

P-Monofer-PREG-01

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	Pharmacosmos A/S
B.1.3.4	Country	Denmark
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	Pharmacosmos A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pharmacosmos A/S
B.5.2	Functional name of contact point	Clinical R & D
B.5.3	Address:
B.5.3.1	Street Address	Roervangsvej 30
B.5.3.2	Town/ city	Holbaek
B.5.3.3	Post code	4300
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+4559485959
B.5.5	Fax number	+4559485962
B.5.6	E-mail	llt@pharmacosmos.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	Monofer
D.2.1.1.2	Name of the Marketing Authorisation holder	Pharmacosmos A/S
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Monofer
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	Ferric derisomaltose
D.3.9.1	CAS number	9004-66-04
D.3.9.2	Current sponsor code	Iron oligosaccharide complex
D.3.9.3	Other descriptive name	IRON(III) ISOMALTOSIDE 1000
D.3.9.4	EV Substance Code	SUB74758
D.3.10	Strength
D.3.10.1	Concentration unit	IU/mg international unit(s)/milligram
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	2000
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Jern C
D.2.1.1.2	Name of the Marketing Authorisation holder	Meda A/S
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	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.3.8	INN - Proposed INN	Ferrous salt
D.3.9.1	CAS number	141-01-5
D.3.9.2	Current sponsor code	Ferrous salt
D.3.9.3	Other descriptive name	FERROUS FUMARATE
D.3.9.4	EV Substance Code	SUB13865MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/mg international unit(s)/milligram
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	12600
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

iron deficiency in pregnant women

E.1.1.1

Medical condition in easily understood language

iron deficiency in pregnant women

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10005329
E.1.2	Term	Blood and lymphatic system disorders
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

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	10002041
E.1.2	Term	Anaemia complicating pregnancy, childbirth, or the puerperium
E.1.2	System Organ Class	10005329 - Blood and lymphatic system 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

The primary objective of the trial is to evaluate and compare the effect of IV iron isomaltoside to a fixed dose of oral iron administered as tablet ferrous fumarate with ascorbic acid as avoidance of developing/having IDA throughout the duration of the trial in pregnant women who have ID after 4 weeks of standard oral treatment.

E.2.2

Secondary objectives of the trial

The secondary objectives are to compare the effect of IV iron isomaltoside and oral ferrous fumarate with ascorbic acid on:
• Hb and other haemathological indices of IDA in maternal blood
• Maternal fatigue
• Maternal Quality of Life (QoL)
• RLS
• Need for an additional IV iron isomaltoside dose rescue medication with IV iron or rescue red blood cell (RBC) transfusion

The safety objective is to compare the safety of iron isomaltoside to oral iron.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Women aged ≥18 years
2. Pregnancy at GA 14+0 - 21+0
3. Ferritin <30 μg/L (0-29 μg/L) after 4 weeks of standard treatment in a clinical setting
4. Willingness to participate and attend all planned follow-up visits, and signing the in-formed consent form

E.4

Principal exclusion criteria

1. History of anaemia caused by e.g. thalassemia, hypersplenism or haemolytic anaemia (known haematologic disorder other than iron deficiency)
2. Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis and haemosiderosis)
3. Drug hypersensitivity (i.e. previous hypersensitivity to IV iron)
4. Known hypersensitivity to any excipients in the investigational drug products
5. History of active asthma within the last 5 years
6. History of multiple allergies
7. Known decompensated liver cirrhosis or active hepatitis
8. Active acute or chronic infections (assessed by clinical judgement)
9. Rheumatoid arthritis with symptoms or signs of active inflammation
10. Treated with IV iron products or blood transfusion within 4 weeks prior to inclusion
11. Treated with erythropoietin (EPO) within 4 weeks prior to inclusion
12. Participation in any other interventional trial where the trial drug has not passed 5 half-lives prior to inclusion
13. Any other medical condition that, in the opinion of the Investigator, may cause the subject to be unsuitable for the completion of the trial or place the subject at potential risk from being in the trial
14. Meeting RBC-transfusion criteria (Hb ≤6.9 g/dL= 4.3 mmol/L with intolerable symptoms of anaemia like severe palpitations, severe dizziness, shortness of breath at rest or syncope or an Hb ≤ 6.4 g/dL (4.0 mmol/L) without intolerable symptoms of anaemia)
15. Multiple pregnancies
16. Inability to read and understand the Danish language

E.5 End points

E.5.1

Primary end point(s)

• Achievement of an Hb ≥11.0 g/dL (≥ 6.8 mmol/L) at all post-baseline time points

E.5.1.1

Timepoint(s) of evaluation of this end point

Any time within 18 weeks after beginning of treatment.

E.5.2

Secondary end point(s)

• Hb ≥11.0 g/dL (≥6.8 mmol/L) at T3w, T6w, T12w, and T18w
• Change in Hb, reticulocytes, reticulocyte haemoglobin content (CHr), s-ferritin, s-transferrin, s-iron, hepcidin, and calculated transferrin saturation (TSAT) from baseline to T3w, T6w, T12w, and T18w
• Incidence of hypophosphatemia (defined as serum [s] phosphate <2 mg/dL) at any time post-baseline to T18w)
• Change in fatigue (FACIT-fatigue scale) from baseline to T3w, T6w, T12w, and T18w
• Change in QoL (Short Form (SF) -12) from baseline to T3w, T6w, T12w, and T18w
• Presence of RLS (using four diagnostic criteria) at T3w, T6w, T12w, and T18w
• Number of subjects who receive an additional IV iron isomaltoside dose at T6w and/or T12w
• Reason for the additional IV iron isomaltoside dose (non-compliance, lack of effect)
• Number of subjects who received 1 or more allogenic RBC-transfusions and the number of units of RBC-transfused per transfused subject from baseline to final subject visit
• Type and incidence of AEs including adverse drug reactions (ADRs) and any suspected unexpected serious adverse events (SUSAR)
• Serious or severe hypersensitivity reaction starting on or after the first dose of randomized treatment (i.e. treatment emergent). The hypersensitivity terms are defined as standardised Medical Dictionary for Regulatory Activities query (SMQ) terms (including four additional terms).
• AEs of special interest: constipation, diarrhoea, flatulence, nausea, vomiting, abdominal pain, dyspepsia, dysguesia, and stool discoloration
• Number of subjects who discontinue from the trial because of lack of response or intolerance of investigational drugs
• Foetal bradycardia related to an additional IV iron isomaltoside infusion at or after GA 26
• Change in biochemical safety parameters from baseline to T3w, T6w, T12w, and T18w
• Compliance to treatment: at baseline in the IV group and by pill-count at T6w and T18w in oral group

In addition, physical examinations and measurements of vital signs, height, weight, and safety laboratory parameters will be measured as part of standard safety assessments.

E.5.2.1

Timepoint(s) of evaluation of this end point

Please see the individual end point in E.5.2

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

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Ferrous fumarate for oral use

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

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:

200

F.1.3

Elderly (>=65 years)

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

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

F.3.3.3

Pregnant women

Yes

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

200

F.4.2

For a multinational trial

F.4.2.1

In the EEA

200

F.4.2.2

In the whole clinical trial

200

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

2017-05-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-04-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-08-18

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