Clinical Trials Register

Summary
EudraCT Number:	2017-001079-22
Sponsor's Protocol Code Number:	ABR57022
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2024-07-22
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

Netherlands - Competent Authority

A.2

EudraCT number

2017-001079-22

A.3

Full title of the trial

A multicenter randomized placebo controlled treatment study of leflunomide in polymyalgia rheumatica

Een multicenter, gerandomiseerde, placebo-gecontroleerde studie van behandeling met leflunomide in polymyalgia rheumatica

A.3.1

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

Treatment with leflunomide in patients with polymyalgia rheumatica

Behandeling met leflunomide in patienten met polymyalgia rheumatica ('spierreuma')

A.3.2

Name or abbreviated title of the trial where available

Leflunomide in PMR

A.4.1

Sponsor's protocol code number

ABR57022

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	University Medical Center Groningen
B.1.3.4	Country	Netherlands
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	Dutch Arthritis Foundation (Reumafonds)
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University Medical Center Groningen
B.5.2	Functional name of contact point	E. Brouwer
B.5.3	Address:
B.5.3.1	Street Address	Hanzeplein 1
B.5.3.2	Town/ city	Groningen
B.5.3.3	Post code	9713 GZ
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31503613432
B.5.6	E-mail	e.brouwer@umcg.nl

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	Leflunomide
D.2.1.1.2	Name of the Marketing Authorisation holder	Mylan BV
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Leflunomide
D.3.4	Pharmaceutical form	Capsule
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	LEFLUNOMIDE
D.3.9.1	CAS number	75706-12-6
D.3.9.4	EV Substance Code	SUB08424MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Polymyalgia Rheumatica

E.1.1.1

Medical condition in easily understood language

Polymyalgia Rheumatica

Polymyalgia Rheumatica ('spierreuma')

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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

To investigate whether the use of leflunomide can prevent relapses during corticosteroid tapering in patients with polymyalgia rheumatica

Kan behandeling met leflunomide relapses voorkomen tijdens afbouwen van glucocorticoiden in patienten met PMR?

E.2.2

Secondary objectives of the trial

1. efficacy with regard to disease activity;
2. glucocorticoid-sparing effect;
3. safety/side-effects over the 24 months of the study

1. vermindering van de ziekte activiteit
2. glucocorticoid-sparing effect
3. veiligheid/bijwerkingen

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Female or male aged ≥ 50 years
2. PMR according to the ACR/EULAR 2012 PMR core (essential) classification criteria
3. Newly diagnosed PMR being on corticosteroids glucocorticoids for less than 4 weeks

1. Vrouwelijke en mannelijke geslacht ≥ 50 jaar
2. PMR volgens de ACR/EULAR 2012 core classificatie criteria
3. Nieuwe PMR behandeld met glucocorticoiden <4 weken

E.4

Principal exclusion criteria

1. Presence of any other connective tissue disease, including vasculitis/giant-cell arteritis
2. PMR on glucocorticoidsglucocorticosteroids for >4 week or >25 mg/day
3. History of alcohol or drug abuse or current alcohol or drug abuse
4. Transplanted organ (except corneal transplant performed more than 3 months prior to screening)
5. Evidence (as assessed by the investigator) of active infection, presence of hepatitis B surface antigen or hepatitis C antibody in blood, HIV positivity.
6. Malignancy within 5 years prior to screening, except for nonmelanoma skin cancer
7. Exposure to DMARD/biological in the last 5 years
8. Pain syndromes, e.g. fibromyalgia, drug-induced myalgia
9. Active thyroid disease
10. Neurological diseases, e.g. Parkinson's disease
11. Contraindications for leflunomide
12. Laboratory abnormalities: renal or hepatic impairment, anemia and significant cytopenia
13. Uncontrolled or poorly controlled hypertension
14. Major surgery or hospitalization within 3 month prior to screening

1. Andere auto-immuun ziekte/systeemziekte, inclusief vasculitis/reuscelarteritis
2. PMR behandeld met glucocorticoiden >4 weken of >25 mg/dag
3. Alcohol of drug abusus heden of in het verleden
4. Orgaantransplantatie
5. Actieve infectie
6. Maligniteit (met uitzondering van non-melanoma huidkanker) <5 jaar voorafgaand aan inclusie
7. DMARD/biological gebruik <5 jaar voorafgaand aan inclusie
8. Pijnsyndroom
9. Actieve schildklierziekte
10. Neurologische ziekten
11. Contraindicaties leflunomide
12. Labafwijkingen: nier- en leverproefstoornissen, anemie en significante cytopenie
13. Slecht geregelde hypertensie
14. Grote chirurgische ingreep of klinische opname <3 maanden voorafgaand aan inclusie

E.5 End points

E.5.1

Primary end point(s)

the time to the first relapse at 12 months

tijd tot de eerste relapse gedurende de eerste 12 maanden

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months

12 maanden

E.5.2

Secondary end point(s)

1. Efficacy with regard to disease activity
2. Glucocorticoid-sparing effect
3. Side-effects during 24 months

1. Verbetering van de ziekteactiviteit
2. Glucocorticoïd-sparing effect
3. 3. Bijwerkingen/veiligheid gedurende 24 maanden

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Efficacy with regard to disease activity
a. time to first relapse within 24 months
b. proportion of patients with a relapse within 12 months and 24 months
c. total number of relapses within 12 months and 24 months
d. time to glucocorticoid-free remission
e. proportion of patients on glucocorticoid-free remission at 6, 12, 18 and 24 months
2. glucocorticoid-sparing effect
a. dose glucocorticoids at 6, 12, 18 and 24 months
b. cumulative dose glucocorticoid at 12, 18, 24 months
3. Side-effects over the 24 months:
a. the number of adverse effects
b. the number of serious adverse events

1. Verbetering van de ziekteactiviteit
a. tijd tot de eerste relapse binnen 24 maanden
b. percentage patienten met een relapse binnen 12 en 24 maanden
c. totale aantal relapses binnen 12 en 24 maanden
d. tijd tot glucocorticoïd-free remissie
2. Glucocorticoïd-sparing effect
a. dosering glucocorticoïd na 6, 12, 18 en 24 maanden
b. cumulatieve dosering glucocorticoïd na 12, 18 en 24 maanden
3. Bijwerkingen/veiligheid gedurende 24 maanden
a. het aantal adverse events
b. het aantal serious adverse events

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

Yes

E.6.13.1

Other scope of the trial description

biomarkers, genetics

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

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

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:

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

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.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

geen

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2024-07-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-03-06

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

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