Clinical Trials Register

Summary
EudraCT Number:	2011-001689-16
Sponsor's Protocol Code Number:	20110531
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:	2013-02-04
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

2011-001689-16

A.3

Full title of the trial

Prospective randomized, double-blind, and placebo-controlled clinical trial with hydroxychloroquine (HCQ) in patients with erosive-inflammatory osteoarthritis (OA) of the finger joints (acronym: OA TREAT)

Multizentrische, prospektive, randomisierte, doppel-blinde und plazebokontrollierte Studie mit Hydroxychloroquin (HCQ) bei Patienten mit erosiv-entzündlicher Fingerpolyarthrose (Akronym: OA TREAT)

A.3.1

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

A prospective study in several sites across Germany with hydroxychloroquine in patients with inflammatory and erosive osteoarthritis of the hands in comparison to placebo over 52 weeks. The patients are randomly assigned to the study arms. Neither doctor nor patient know which treatment the patient receives. Acronym: OA TREAT.

Eine deutschlandweite, prospektive, Studie mit Hydroxychloroquin bei entzündlich-erosiver Fingerpolyarthrose im Vergleich zur Behandlung mit einem Scheinmedikament (Plazebo) über 52 Wochen. Die Patienten werden zufällig den Studienarmen zugeordnet, wobei weder der Arzt noch der Patient wissen, welche Behandlung der Patient erhält. Akronym: OA TREAT

A.3.2

Name or abbreviated title of the trial where available

OA TREAT

A.4.1

Sponsor's protocol code number

20110531

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN46445413

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1121-1623

A.5.4

Other Identifiers

Name:

German Register of Clinical Trials

Number:

DRKS00000796

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	Charité - Universitätsmedizin Berlin
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	Federal Ministry of Education and Research
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	Charité - Universitätsmedizin Berlin
B.5.2	Functional name of contact point	Dep. of Rheumatology, CC12
B.5.3	Address:
B.5.3.1	Street Address	Charitéplatz 1
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	10117
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4930450513133
B.5.5	Fax number	+4930450513982
B.5.6	E-mail	insider@charite.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	Quensyl
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Aventis
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.3.1	Product name	Hydroxychloroquine
D.3.2	Product code	6584604.00.00
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.3.11 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

inflammatory and erosive osteoarthritis of the finger joints and hand

entzündlich-erosive Fingerpolyarthrose

E.1.1.1

Medical condition in easily understood language

active, inflammatory and erosive arthrosis of the finger joints

aktivierte, entzündliche und erosive Arthrose der Fingergelenke

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	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10019115
E.1.2	Term	Hand osteoarthritis
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

The aim of this study is to investigate efficacy and safety of HCQ by clinical and radiological outcome compared to placebo in patients with severe and refractory inflammatory hand OA.

Ziel dieser Studie ist es, den Effekt und die Sicherheit von
Hydroxychloroquin, gemessen anhand von klinischen und radiologischen Parametern, bei Patienten mit einer schweren entzündlichen und refraktären Fingerpolyarthrose im
Vergleich zu Plazebo zu erforschen

E.2.2

Secondary objectives of the trial

not applicable

Sekundäre Ziele sind nicht definiert.

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

1. Evaluation of the dental health in patients with inflammatory-erosive hand osteoarthritis
Date: 08-12-2015
Version: 6.0
Objectives:Evaluation of the dental health by means of a questionnaire. Determination of antibodies against oral bacteria by blood analysis.

2. Determination of the blood concentration of pyrophosphate and syndecan-4 in patients with erosive-inflammatory hand osteoarthritis.
Date: 08-12-2015
Version: 6.0
Objectives: Evaluation of new biomarker in erosive osteoarthritis of finger joints

3. Evaluation of neuroimmunoendocrinological serological biomarker in patients with erosive osteoarthritis of finder joints.
Date: 08-12-2015
Version: 6.0
Objectives: Evaluation and description of neuroimmunoendocrinological serological biomarker in inflammation osteoarthritis as part of disease activity.

1.Evaluation der Zahngesundheit bei Patienten mit einer erosiv-entzündlicher Fingerpolyarthrose.
Datum: 08-12-2015
Version: 6.0
Ziel: Evaluation der Zahngesundheit mittels eines Fragebogens und Bestimmung von oralen bakteriellen Antikörper.

2. Bestimmung der Pyrophosphatkonzentrationen und Syndekan-4 im Blut bei Patienten mit einer erosiv-entzündlicher Fingerpolyarthrose.
Datum: 08-12-2015
Version: 6.0
Ziel: Untersuchung neuer Biomarker der erosiven Arthrose der Fingergelenke

3. Evaluation neuroimmunoendokrinologische serologischer Biomarker bei der der entzündlichen Arthrose der Fingergelenke.
Datum: 08-12-2015
Version: 6.0
Ziel:Evaluation und Beschreibung neuroimmunoendokrinologische serologischer Biomarker bei der der entzündlichen Arthrose der Fingergelenke als Ausdruck der Krankheitsaktität.

E.3

Principal inclusion criteria

1) Men and women from 40 to 80 years.
2) Presence of clinical inflammatory hand OA according to ACR criteria.
3) Conforming to the ACR criteria for hand OA supported by X - ray of both hands, dating less than 6 months ago, X - ray of the hands showing radiological
signs of digital erosive OA in one or more joints. This
criterion is checked by a central assessment.
4) Symptoms of digital inflammatory OA (pressure pain of the joints and/or florid joint swelling and/or redness and/or warmth) with more than 3 finger joints for more than 3 months despite taking analgesics and NSAIDs. An existing medication with NSAIDs/coxibs should be continued according to the individual need two weeks prior to study entry.
5) Pain above 4 as evaluated by the AUSCAN - NRS (0 – 10),
6) Function as co-primary clinical outcome with ≥ 26 using the AUSCAN.
7) The ability to understand the trial information for patients (AMG §40 (1) and 3b),
8) The ability to sign the informed consent form including written the data protection form (according §40 (1) and 3b AMG)

1) Männer und Frauen von 40 bis 80 Jahre.
2) Klinischer Nachweis einer OA der Hände nach den ACR-Kriterien.
3) Radiologischer Nachweis einer erosiven OA der Hände anhand der Befundung von Röntgenbildern, die nicht älter als 6 Monate sind. Die Hände müssen radiologische Zeichen einer digitalen erosiven OA aufweisen. Dieses Einschlusskriterium wird durch
eine einheitliche zentrale Befundung überprüft.
4) Symptome der entzündlichen OA (Druckschmerz der Gelenke und/oder floride Gelenkschwellung und/oder Rötung und/oder Überwärmung) an mehr als drei Fingern mit einem Analgetika- oder NSAR - Bedarf über mehr als drei Monate. Eine bestehende Medikation mit NSAR/Coxiben sollte entsprechend des individuellen Bedarfs zwei Wochen vor Studieneinschluss fortgeführt werden.
5) Schmerzen in den Händen ≥ 4 auf einer NRS - Skala (0 – 10),
6) Funktionseinschränkung der Hände gemessen mit dem
AUSCAN ≥ 26.
7) Fähigkeit, die Patienteninformation zu verstehen.
8) Schriftliche Einwilligung (laut AMG §40 (1) 3b) und Einwilligung zur Datenspeicherung.

E.4

Principal exclusion criteria

1) Patients who are currently treated with HCQ or have received HCQ in the past due to OA of the hands already.
2) Patients who have not been tolerated HCQ (e.g. skin disease or malaria prophylaxis) or patients who HCQ was discontinued due to an eye disease (eg. by an ophthalmologist).
3) Existence of painful syndrome of upper limbs likely to interfere with the monitoring of pain.
4) Patients suffering or having suffered from secondary OA after one of the following diseases [e.g. Infectious arthritis, Acromegaly,
Ochronosis, Hemochromatosis, Gout, etc.] or inflamematory
joint diseases.
5) Any unstable medical condition which would expose the patient to an unacceptable risk.
6) Planned Surgery.
7) Local injection (i.a.; i.m.) of finger- or hand joints with glucocorticoids or other medications within the previous three months.
8) Current intake of oral or systemic glucocorticoids.
9) Presence of retinopathy.
10) Known hypersensitivity to HCQ or to one of the drug in this study protocol and treatment with digoxine.
11) Other serious clinical situations that expose the patient at risk of the opinion of the local investigator.
12) Current participation in another clinical trial or taking an
experimental treatment.
13) Patients who are underage or are incapable to understand the aim, importance and consequences of the study and to give legal informed consent (according to §40 Abs. 4 and §42 Abs. 2 and Abs. 3 AMG).
14) Prisoners, and persons who are institutionalized due to regulatory or judical order (according to AMG §40(1), no. [4].
15) Pregnant and breastfeeding women
16) Have had lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of recurrence for at least 5 years prior to screening.

1) Patienten, die aktuell mit HCQ-Behandlung behandelt werden oder in der Vergangenheit aufgrund einer OA der Hände bereits erhalten haben.
2) Patienten, die HCQ bereits nicht vertragen haben (z.B. im
Rahmen einer Hauterkrankung oder einer Malariaprophylaxe)
bzw. aufgrund einer Augenerkrankung bereits abgesetzt worden ist (bspw. durch den Augenarzt).
3) Existierende Schmerzsyndrome der oberen Extremität, die mit
der OA-Schmerzangabe interferieren können.
4) Patienten mit einer sekundären OA aufgrund folgender Erkrankungen
(z.B. Infektiöse Arthritis, Akromegalie, Ochronosis,
Hämochromatose, Gicht, etc.) oder infolge entzündlicher Gelenkerkrankungen.
5) Andere nichtbehandelte medizinische Erkrankungen, die für den Patienten ein unakzeptables Risiko darstellen.
6) Geplante Operationen.
7) Lokale Injektionen (i.a., i.m.) von Glukokortikoiden oder anderen Medikamenten in den letzten drei Monaten Finger - und Handgelenken.
8) Aktuelle orale oder andere systemische Behandlung mit
Glukokortikoiden.
9) Vorhandensein einer Retinopathie.
10) Bekannte Überempfindlichkeit gegen HCQ oder ein anderes im
Studienprotokoll empfohlenes Medikament (z.B. NSAR, Coxibe,
Paracetamol) als auch die Behandlung mit Digoxin.
11) Andere schwerwiegende klinische Situationen, die nach Einschätzung des lokalen Prüfarztes den Patienten einem Risiko aussetzen.
12) Aktuelle Teilnahme an einer anderen Studie oder Einnahme
einer experimentellen Therapie.
13) Minderjährige und Erkrankungen, die das Verständnis des
Untersuchungsprotokolls einschränkt (nicht einwilligungsfähig).
14) Gefängnisinsassen sowie alle Personen, die aufgrund einer behördlichen oder gerichtlichen Anordnung in Anstalten untergebracht sind [vgl. AMG §40(1), Nr. [4].
15) Schwangere und stillende Frauen
16) Patienten, die ein Lymphom, eine Leukämie haben oder eine maligne Erkrankung in den letzten fünf Jahren hatten bzw. keine komplette Remission der malignen Erkrankung erreicht haben. Davon ausgenommen sind das Basalzellkarzinom (Basaliom)
oder Plattenepithelkarzinome der Haut, ohne Zeichen eines rekurrierenden Verlaufes über einen Zeitraum von mindestens fünf Jahren vor dem Screening.

E.5 End points

E.5.1

Primary end point(s)

Primary clinical endpoint: Australian-Canadian OA Index (AUSCAN, German version) for pain, and hand disability as co-primary clinical outcome at week 52.

Primärer klinischer Endpunkt: Australian-Canadian OA Index (AUSCAN, Deutsche Version) für Schmerzen und Handfunktion zur Woche 52.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 52.

Woche 52.

E.5.2

Secondary end point(s)

• Efficacy of HCQ with related to AUSCAN to patient’s global assessment of disease activity, patient’s assessment of stiffness, and physician’s global assessment of disease activity from baseline to week 26, 52.
• Radiographic progression from baseline to week 52.
• Comparison of pain, functioning, disability, quality of life, patient-acceptable symptoms and health with SACRAH, HAQ, SF-36,from baseline to week 26, 52.
• Assessment and comparison of the inflammatory status using the following parameters: joint pain and joint swelling, night pain, morning stiffness, local erythema/redness, CRP- and ESR-levels from baseline to week 26, 52.
• Comparison of the increase or decrease of the consumption in the standard medication in the last 7 days before each visit (NSAIDs, coxibs).

• Wirksamkeit von HCQ ermittelt sowohl mit dem AUSCAN Scores für Schmerzen und Funktion von der Baseline zur Woche 26 als auch mit der globalen Patienteneinschätzung der Krankheitsaktivität, der Schmerzen, der Gelenksteifigkeit und der globalen ärztlichen Einschätzung der Krankheitsaktivität von der Baseline zur Woche 26 und 52.
• Radiologische Progression zwischen Baseline und Woche 52.
• Vergleich der Schmerzen, Funktion, Behinderung, Lebensqualität der Patienten ermittelt mit dem SACRAH, HAQ, SF–36, AUSCAN von der Baseline zur Woche 26 und 52.
• Erhebung und Vergleich des Entzündungsstatus durch Nutzung folgender Parameter: Gelenkschmerzen, Gelenkschwellungen, nächtlicher Schmerz, Morgensteifigkeit, lokales Erythem/Rötung, CRP- und BSG-Werte von der Baseline zur Woche 26 und 52.
• Vergleich der Ab- oder Zunahme des Verbrauches an Standardmedikation der letzten 7 Tage vor jeder Visite (NSAR, Coxibe).

E.5.2.1

Timepoint(s) of evaluation of this end point

From baseline to week 13, 26, 39 and 52.

Von der Baseline zur Woche 13, 26, 39, 52.

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)

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

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:

101

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

101

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2013-02-04.

Yes

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

202

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)

The treatment after the subject has ended his/her participation is the
standard of medical treatment in hand osteoarthritis with nonsteroidal
anti-inflammatory drugs, coxibs, analgesics, opiates and ergo-/physiotherapy.

Die Behandlung nach Studienende umfasst den Standard der
medizinischen Behandlung bei Fingerpolyarthrose mit nichtsteroidalen
Antirheumatika, Coxibe, Analgetika, Opiate und Ergo-/Physiotherapie.

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

2013-06-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-04-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-07-05

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