Clinical Trials Register

Summary
EudraCT Number:	2019-004583-22
Sponsor's Protocol Code Number:	IDRLS
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-05-07
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

Austria - BASG

A.2

EudraCT number

2019-004583-22

A.3

Full title of the trial

Prospective analysis of the therapeutic efficacy of iron isomaltoside in combination with or without dopaminergic therapy in patients with restless legs syndrome

A.3.1

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

Evaluation of positive effects of iron treatment for patients with the restless legs syndrome, who either received dopaminergic therapy before or not.

A.3.2

Name or abbreviated title of the trial where available

IDRLS

A.4.1

Sponsor's protocol code number

IDRLS

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	Medical University of Innsbruck
B.1.3.4	Country	Austria
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	Medical University of Innsbruck
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medical University
B.5.2	Functional name of contact point	Kompetenzzentrum Klinische Studien
B.5.3	Address:
B.5.3.1	Street Address	Anichstraße 35
B.5.3.2	Town/ city	Innsbruck
B.5.3.3	Post code	6020
B.5.3.4	Country	Austria
B.5.6	E-mail	barbara.lanthaler@i-med.ac.at

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 100mg/ml Lösung zur Injektion und Infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Pharmacosmos A/S
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	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.3.9.3	Other descriptive name	Monofer 100mg/ml solution for injection/infusion
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1 to 500
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	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

Restless leg syndorme

E.1.1.1

Medical condition in easily understood language

Restless leg syndrome

E.1.1.2

Therapeutic area

Not possible to specify

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary objective of this study is to investigate the effect of iron supplementation or placebo (in combination or not with dopaminergic therapy) on clinical RLS symptoms measured by the IRLS.

E.2.2

Secondary objectives of the trial

Secondary objectives are to investigate the effect of iron supplementation a. on clinical RLS symptoms measured by other validated scales, b. on the mitochondrial respiration and serological biomarkers, and c. on iron content in the substantia nigra.

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

- Changes in mitochondrial respiration of selected and randomly assigned patients measured with OROBOROS respirometry
- Changes in iron content in the substantia nigra detected by an MRI in a subgroup of 80 patients

E.3

Principal inclusion criteria

Inclusion criteria:
1. RLS diagnosed according to the current IRLSSG criteria
Essential diagnostic criteria (all must be met):
- An urge to move the legs usually but not always accompanied by, or felt to be caused by, uncomfortable and unpleasant sensations in the legs.
- The urge to move the legs and any accompanying unpleasant sensations begin or worsen during periods of rest or inactivity such as lying down or sitting.
- The urge to move the legs and any accompanying unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues.
- The urge to move the legs and any accompanying unpleasant sensations during rest or inactivity only occur or are worse in the evening or night than during the day.
- The occurrence of the above features is not solely accounted for as symptoms primary to another medical or a behavioral condition (e.g. myalgia, venous stasis, leg edema, arthritis, leg cramps, positional discomfort, habitual foot tapping).
2. Female and male participants aged ≥ 18 years
3. Negative urine/serum pregnancy test in women of childbearing potential (WOCBP, see section 7.6). WOCBP who are sexually active, agree to use highly effective means of contraception during the study and for at least 1 month post-study treatment. Allowed are accepted and effective hormonal/non-hormonal methods of contraception and sexual abstinence or vasectomised partners (> 3 months previously). Vasectomy has to be confirmed by two negative semen analyses.
4. Written, signed and dated informed consent

E.4

Principal exclusion criteria

Exclusion criteria:
1. Secondary RLS
2. Sporadic RLS
3. Dialysis-dependent renal failure (eGFR < 20 mL/min/1.73m2)
4. Moderate or severe heart failure (NYHA III-IV)
5. Malignancies
6. Pregnancy and breastfeeding
7. Known Thalassaemia minima/minor, hemochromatosis, polycythemia vera, hemolytic anemia
8. Current intake of opiates
9. Iron substitution, erythropoietin therapy or blood transfusion in the previous 6 months
10. Ferritin > 200 mg/dL or Transferrin Saturation over 45%
11. Phosphate levels below the lower limit normal before study drug initiation.
12. Contraindications for performing a MRI (for example claustrophobia, pacemakers, metal implants).
13. Body weight < 50 kg
14. Known Hypersensitivity to the active substance or any of its excipients (Sodium hydroxide/Hydrochloric acid)
15. Participating in another interventional study

E.5 End points

E.5.1

Primary end point(s)

- Changes in RLS severity as detected by the IRLS

E.5.1.1

Timepoint(s) of evaluation of this end point

at the end of trial

E.5.2

Secondary end point(s)

1. Changes in RLS severity as detected by the sIRLS, RLS-6 and CGI
2. Changes in blood count, iron, Tf, TSAT, ferritin, sTfR, hepcidin-25, creatinine (GFR), GPT, GOT, LDH, CRP, electrolytes (Na, K, P, Ca), PTH, LCN2, dopamine, 1,25-(OH)2 vitamin D, 25-OH vitamin D, EPO, ERFE, PDGF-BB, LCN2 and metabolites (ATP, NADH/NAD, Lactate, Succinate, Citrate, Pyruvate, free fatty acids)
3. Changes in mitochondrial iron and Krebs cycle metabolism gene expression in monocytes detected by RT-PCR
4. Changes in mitochondrial respiration of selected and randomly assigned patients measured with OROBOROS respirometry
5. Changes in iron content in the substantia nigra detected by an MRI in a subgroup of 80 patients (20 dopaminergic therapy/iron, 20 dopaminergic therapy/placebo, 20 no previous treatment/iron and 20 no previous treatment/placebo)

E.5.2.1

Timepoint(s) of evaluation of this end point

at the end of trial

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)

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

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

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:

120

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

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

140

F.4.2

For a multinational trial

F.4.2.1

In the EEA

140

F.4.2.2

In the whole clinical trial

140

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)

standard treatment

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

2021-06-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-06-07

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

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