Clinical Trials Register

Summary
EudraCT Number:	2009-016728-29
Sponsor's Protocol Code Number:	P-Monofer-CKD-02
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-07-13
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

Germany - BfArM

A.2

EudraCT number

2009-016728-29

A.3

Full title of the trial

A Phase III, Randomized, Comparative, Open-label Study of Intravenous Iron Isomaltoside 1000(Monofer®) administered by Infusions or Repeated Bolus Injections in Comparison with Oral Iron Sulphate in Subjects with Non-Dialysis Dependent Chronic Kidney Disease and with Renal-Related Anaemia.

A.3.1

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

A Phase III study where Iron Isomaltoside 1000 (Monofer®) administered by infusions or repeated bolus injections is compared with Iron Sulphate taken by mouth in subjects with non-dialysis dependent chronic kidney disease and with renal-related anaemia.

A.3.2

Name or abbreviated title of the trial where available

P-Monofer-CKD-02

A.4.1

Sponsor's protocol code number

P-Monofer-CKD-02

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01102413

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	VP, CMO (Lars Lykke Thomsen)
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	+4559485935
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 100 mg/ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Pharmacosmos A/S
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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 infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent) Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Iron Isomaltoside 1000
D.3.9.1	CAS number	9004-66-4
D.3.9.3	Other descriptive name	iron isomalto-oligosaccharide complex
D.3.9.4	EV Substance Code	SUB14268MIG
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	100
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	Ferro Duretter, prolonged release tablet
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline Consumer Healthcare AB
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	Ferro Duretter, prolonged release tablet
D.3.4	Pharmaceutical form	Prolonged-release 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 sulphate
D.3.9.3	Other descriptive name	FERROUS SULPHATE
D.3.9.4	EV Substance Code	SUB11967MIG
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	100
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

Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD) associated with renal-related anaemia

E.1.1.1

Medical condition in easily understood language

Patient having anemia due to a chronic kidney disease. Patient is not depending on dialysis

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	15.1
E.1.2	Level	LLT
E.1.2	Classification code	10064848
E.1.2	Term	Chronic kidney disease
E.1.2	System Organ Class	100000004857

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.1
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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate that intravenous iron isomaltoside 1000 (Monofer®) is non-inferior to oral iron sulphate in reducing renal related anemia in subjects with non-dialysis dependent chronic kidney disease (NDD-CKD), determined as ability to increase Hb

E.2.2

Secondary objectives of the trial

1. To assess other relevant haematology and biochemical parameters during the study.
2. Quality of Life (QoL) assessment by Linear Analog Scale Assessment (LASA).
3. To assess safety of intravenous iron isomaltoside 1000 (Monofer®) compared to oral iron sulfate.
4. Assessment of RLS symptoms and change in these symptoms during the study.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Men and women, aged more than 18 years.
2. Subjects diagnosed with NDD-CKD with MDRD calculated eGFR between 15-59 mL/min.
3. Hb < 11.0 g/dL (6.80 mmol/L).
4. Either or both of the following iron stores indicators below target [Serum ferritin < 200 ug/l and Transferrin Saturation (TfS) < 20%].
5. Life expectancy beyond 12 months by Principal Investigator‟s judgement.
6. Willingness to participate after informed consent and any authorization as required by local law
(e.g. Protected Health Information [PHI] for North America).

E.4

Principal exclusion criteria

1. Anaemia predominantly caused by factors other than renal impairment or iron deficiency (according to Principal Investigator’s judgment).
2. Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis and haemosiderosis).
3. Drug hypersensitivity (i.e. previous hypersensitivity to Iron Dextran or iron mono- or disaccharide complexes or to iron sulphate or any excipients of the study drug.
4. Subjects with history of multiple allergies.
5. Decompensated liver cirrhosis or active hepatitis (Alanine Aminotransferase (ALT) > 3 times upper normal limit).
6. Active acute or chronic infections ((assessed by clinical judgment), supplied with White Blood Cells (WBC) and C-Reactive Protein (CRP)).
7. Rheumatoid arthritis with symptoms or signs of active joint inflammation.
8. Pregnancy and nursing (To avoid pregnancy, women have to be postmenopausal (at least 12 months must have elapsed since last menstruation), surgically sterile, or women of child bearing potential must use one of the following contraceptives during the whole study period and after the study has ended for at least 5 times plasma biological half-life of the investigational medicinal product (5 days): Contraceptive pills, intrauterine devices (IUD), contraceptive depot injections (prolonged-release gestagen), subdermal implantation, vaginal ring, and transdermal patches).
9. Extensive active bleeding necessitating blood transfusion.
10. Planned elective surgery during the study.
11. Participation in any other clinical study within 3 months prior to screening.
12. Known intolerance to oral iron treatment.
13. Untreated B12 or folate deficiency.
14. I.V. or oral iron treatment or blood transfusion within 4 weeks prior to screening visit.
15. ESA treatment within 8 weeks prior to screening visit.
16. Serum ferritin > 500 μg/L.
17. Any other medical condition that, in the opinion of Principal Investigator, may cause the subject to be unsuitable for the completion of the study or place the subject at potential risk from being in the study or interfere with study drug evaluation. Example, Uncontrolled Hypertension, Unstable Ischemic Heart Disease or Uncontrolled Diabetes Mellitus.
18. Body weight < 30 kilograms.

E.5 End points

E.5.1

Primary end point(s)

Change in Hb concentrations from baseline to week 4

E.5.1.1

Timepoint(s) of evaluation of this end point

From baseline to week 4.

E.5.2

Secondary end point(s)

1. Number of subjects who have change in Hb concentration ≥ 1.0 g/dL from baseline to week 2, 4 or 8.
2. Number of subjects who have change in Hb concentration ≥ 2.0 g/dL from baseline to week 2, 4, or 8.
3. Number of subjects who have Hb > 11 g/dl (6.80 mmol/L), have serum ferritin (200-800μg/L) and have achieved Transferrin saturation (TfS) (20-50 %) at weeks 2, 4 or 8.
4. Change in Hb concentration from baseline to week 2 and 8.
5. Change in concentrations of serum iron, serum ferritin, TfS and TIBC from baseline to week 1, 2, 4 and 8.
6. Number of subjects who discontinue study because of lack of response or need for blood transfusion or intolerance of investigational drugs.
7. Change in total QoL score (LASA) from baseline to week 4 and 8.
8. Change in eGFR from baseline to week 8.
9. Change in RLS symptoms (CH-RLSq score) from baseline to week 8 in subjects with RLS symptoms at baseline.
10. Number of subjects who experience any Adverse Drug Reaction (ADR) including any Suspected Unexpected Serious Adverse Reaction (SUSAR).
11. Number of adverse events of special interest (i.e. hypersensitivity reactions or hypotension at pre-specified time points in relation to administration of study drug).

E.5.2.1

Timepoint(s) of evaluation of this end point

Time point(s) are specified under each secondary endpoint.

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

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

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

Denmark

Germany

India

Ireland

Poland

Romania

Russian Federation

United Kingdom

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

Last Participant Last Visit is either the date of the last visit of the last participant to complete the study, or the date at which the last data point from the last participant, which was required for statistical analysis (i.e. key safety and efficacy results for decision making), was received, whichever is the later date.

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:

315

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

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

115

F.4.2.2

In the whole clinical trial

350

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)

After the end of the study or if participant is withdrawn from the study, the participant will be treated according to
standard hospital practice.

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

2012-08-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-08-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-04-25

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