Clinical Trials Register

Summary
EudraCT Number:	2020-000624-20
Sponsor's Protocol Code Number:	ILONA
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-04-26
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

Germany - BfArM

A.2

EudraCT number

2020-000624-20

A.3

Full title of the trial

Core decompression versus core decompression followed by infusion of Iloprost in the
treatment of non-traumatic avascular necrosis of the femoral head

A.3.1

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

Core decompression versus core decompression followed by infusion of Iloprost in the
treatment of non-traumatic avascular necrosis of the femoral head

A.3.2

Name or abbreviated title of the trial where available

ILONA

A.4.1

Sponsor's protocol code number

ILONA

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	Leipzig University
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	Deutsche Forschungsgemeinschaft (DFG)
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Universität Leipzig
B.5.2	Functional name of contact point	ZKS Leipzig
B.5.3	Address:
B.5.3.1	Street Address	Haertelstr. 16-18
B.5.3.2	Town/ city	Leipzig
B.5.3.3	Post code	04107
B.5.3.4	Country	Germany
B.5.4	Telephone number	4934197 16247
B.5.5	Fax number	4934197 16259
B.5.6	E-mail	ilona@zks.uni-leipzig.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	Iloprost ratiopharm
D.2.1.1.2	Name of the Marketing Authorisation holder	ratiopharm GmbH
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	Concentrate for 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	Iloprost
D.3.9.1	CAS number	78919-13-8
D.3.9.4	EV Substance Code	SUB08136MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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 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

non-traumatic avascular necrosis of the femoral head (N-ANFH)

E.1.1.1

Medical condition in easily understood language

non-traumatic avascular necrosis of the femoral head (N-ANFH)

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10003860
E.1.2	Term	Avascular necrosis femoral head
E.1.2	System Organ Class	100000004859

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 the ILONA trial is to show that in patients with non-traumatic avascular necrosis of the femoral head treatment with Iloprost for 10 days in addition to core decompression is more effective compared to core decompression alone with regard to functional outcome assessed by the Harris Hip Score (HHS) after 12 months.

E.2.2

Secondary objectives of the trial

To describe and compare outcome measures between the two strategies: Iloprost for 10 days in addition to core decompression versus core decompression alone.
Time to event endpoint:
• Time to indication to total hip arthroplasty (THA), measured
from randomisation up to one year,
MRI based endpoints:
• MRI confirmed subchondral fracture (crescent sign and/or break-down of subchondral bone plate) after 3 and 12 months.
• Appearance of MRI-confirmed bone marrow oedema (BME) and / or necrosis after 3 and 12 months.
Outcome scores:
• Western Ontario and McMaster University Osteoarthritis
Index (WOMAC) after 3, 6 and 12 months
• SF-36 after 3, 6 and 12 months
• iHOT33 after 3, 6 and 12 months

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. non-traumatic avascular necrosis of the femural head
2. Core Lab evaluation: ARCO stage I or II diagnosed and confirmed by:
a. X-ray of both sides of the hip (Pelvis overview and both sides of the hip in Lauenstein position)
AND
b. MRI of both sides of the hip
Note: In patients where both hips are affected, the clinically more severely affected hip should be considered for inclusion.
3. Age 18 - 65 years (for patients older than 50 years the differential diagnosis rapidly destructive osteoarthritis must be ruled out)
4. body weight 50 - 110 kg
5. Written informed consent

E.4

Principal exclusion criteria

1. Patients with N-ANFH of one of the following known aetiologies
a. Ongoing Chemotherapy or chemotherapy within the last 12 months
b. Ongoing alcohol abuse (anamnestic assessment) or alcohol abuse within the last 6 months
c. Renal insufficiency [GFR <50ml/min/1,73m2 (compensated renal insufficiency) or <60ml for the duration of more than three months]
d. Kidney transplantation within the last 12 months
e. Sickle cell anaemia
f. Gaucher’s dieseas (Morbus Gaucher)

2. Patients who previously underwent core decompression on one side of the hip
3. Patients previously treated with Iloprost
4. Contraindications to Iloprost such as hypersensitivity to Iloprost or its excipients (Trometamol, Ethanol 96%, sodium chloride, hydrochloric acid)
5. Situations or parallel treatment in which the effect of the drug on the platelets could increase the risk of bleeding complications (e.g. active peptic ulcer, trauma, intracranial hemorrhage, treatment with NSAR in the last 4 days (or longer until the 5-fold half-life is reached)
6. Severe coronary heart disease or unstable angina
7. Myocardial infarction within the last six months
8. Decompensated cardiac failure if not under close medical supervision
9. Severe arrhythmias
10. Suspected pulmonary congestion
11. Cerebrovascular events (e.g. transient ischaemic attack, stroke) within the last three months
12. Acute or chronic congestive heart failure staged NYHA II-IV
13. Pulmonary hypertension due to venous occlusive disease
14. Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension
15. Liver cirrhosis
16. Infection with SARS-2-CoV requiring hospitalisation in the last seven weeks prior to core decompression
17. Known vascular aneurysm
18. Fertile women (within two years of their last menstruation) without appropriate contraceptive measures (implanon, injections, oral contraceptives, intrauterine devices, partner with vasectomy) while participating in the trial (participants using a hormone-based method have to be informed of possible effects of the trial medication on contraception).
19. Previous participation in the ILONA trial
20. Participation in other interventional trials
21. Patients under legal supervision or guardianship
22. Physiological, psychological/mental or other inabilities to supply required information (e.g. fill out the questionnaire due to dementia, language difficulties, ...).
23. Suspected lack of compliance
24. Pregnant or nursing women (negative pregnancy test is required)

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the Harris Hip Score (HHS) after 12 months.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months after randomisation

E.5.2

Secondary end point(s)

Time to event endpoint:
• Time to total hip arthroplasty (THA), measured from randomisation up to one year (main secondary endpoint)
MRI based endpoints:
• MRI confirmed subchondral fracture (crescent sign and/or break-down of subchondral bone plate) after 3 and 12 months (main secondary endpoint)
• Appearance of MRI-confirmed bone marrow oedema (BME) and / or necrosis after 3 and 12 months.
Outcome scores:
• Western Ontario and McMaster University Osteoarthritis Index (WOMAC)
after 3, 6 and 12 months
• SF-36 after 3, 6 and 12 months
• iHOT-33 (international hip outcome tool, long form) after 3, 6 and 12 months

E.5.2.1

Timepoint(s) of evaluation of this end point

(3), (6) and 12 months after randomisation

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

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

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

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

last patient last visit

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:

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

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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

2021-06-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-06-08

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

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