Clinical Trials Register

Summary
EudraCT Number:	2017-003425-15
Sponsor's Protocol Code Number:	2017
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2017-09-12
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2017-003425-15

A.3

Full title of the trial

Patients with rheumatoid arthritis and synovitis treated with ultrasound guided intraarticular or intramuscular glucocorticoid injection - A randomised, double-blind, controlled study (Panguian)

Patienter med reumatoid artrit og led hævelse, behandlet med ultralyds-guided lokal intraartikulær eller intramuskulær glucocorticoid injektion - Et randomiseret dobbeltblindet studie (Panguian)

A.3.1

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

Patients with rheumatoid arthritis and synovitis treated with ultrasound guided intraarticular or intramuscular glucocorticoid injection - A randomised, double-blind, controlled study (Panguian)

Patienter med ledegigt og led hævelse, behandlet med ultralyds-guided lokal binyrebark injektion i led eller muskulær - Et randomiseret dobbeltblindet studie (Panguian)

A.4.1

Sponsor's protocol code number

2017

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	Videncenter for Reumatologi og Rygsygdomme, Rigshospitalet
B.1.3.4	Country	Denmark
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	idencenter for Reumatologi og Rygsygdomme, Rigshospitalet
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	Videncenter for Reumatologi og Rygsygdomme, Rigshospitalet
B.5.2	Functional name of contact point	Indgang 5, stuen
B.5.3	Address:
B.5.3.1	Street Address	Valdemar Hansens Vej 17
B.5.3.2	Town/ city	Glostrup
B.5.3.3	Post code	2600
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+4438 63 25 99
B.5.6	E-mail	maj-brit.thyme.havlit@regionh.dk

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	Diprofos Depot
D.2.1.1.2	Name of the Marketing Authorisation holder	Orifarm a/s
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.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intraarticular use Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BETAMETHASONE ACIBUTATE
D.3.9.1	CAS number	5534-05-4
D.3.9.2	Current sponsor code	Glucococorticoid
D.3.9.3	Other descriptive name	Binyrebsrkhormon
D.3.9.4	EV Substance Code	SUB05798MIG
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	3.5 to 14
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 injection/infusion
D.8.4	Route of administration of the placebo	Intraarticular use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection/infusion
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Treatment of synovitis among rheumatoid arthritis patients

Behandling af led hævelse hos leddegigt patienter

E.1.1.1

Medical condition in easily understood language

Treatment of swollen joints

Behandling af hævede led

At belyse om UL-guided glucocorticoid intraartikulært injektion har bedre effekt end im. glucocorticoid injektion hos patienter med synovit

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	21.0
E.1.2	Level	PT
E.1.2	Classification code	10042868
E.1.2	Term	Synovitis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Explore whether ultrasound-guided intra-articular glucocorticoid injection in the joint has better effect than intramuscularly glucocorticoid injection among patients with synovitis, assessed by US examination, clinical evaluation and patients reported outcomes

At belyse om UL-guided glucocorticoid intraartikulært injektion har bedre effekt end im. glucocorticoid injektion hos patienter med synovit, vurderet ved hjælp af UL, klinisk vurdering og deltager rapporterede outcomes.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Treatment demanding synovitis in up to 4 joints, defined as clinical assessed swollen joint and US grey scale og Doppler score ≥1, in following joints: interphalangeal(IP)-, proximal interphalangeal (PIP)-, metacarpophalangeal(MCP)-, wrist- (radiocarpal-intercarpal and/or ulnacarpal), ankle- and metatarsophalangeal(MTP).

Rheumatoid arthritis according to ACR/EULAR 2010 criteria

Above 18 years of age

Behandlingskrævende synovit i op til 4 led, defineret som et klinisk hævet led samt en UL grey scale og Doppler score ≥1, i følgende led: interphalangeal(IP)-, proximal interphalangeal (PIP)-, metacarpophalangeal(MCP)-, hånd- (radiocarpal-intercarpal og eller ulnacarpal), ankel- og metatarsophalangeal(MTP) 2-5 led

Reumatoid artrit I henhold til ACR/EULAR 2010 kriterier.

Alder over 18 år.

E.4

Principal exclusion criteria

Start of Disease-modifying anti-rheumatic drugs (DMARDs) / biological treatment within the last 12 weeks
Change of DMARDs treatment within the last 6 weeks.
Change of glucocorticoid treatment within the last 6 weeks.
Start of Non-Steroidal Anti-Inflammatory Drugs (NSAID) treatment within the last 10 days.
Chronic synovitis in the same IP-, PIP-, MCP-, wrist-, ankle- and MTP 2-5 joints, is defined as either severe destructive erosions, assessed by previously x-rays or persistent synovitis (6 months) despite >1 local joint injection with glucocorticoid according to DANBIO or journal registrations.
Treatment demanding synovitis in more than 4 joints, defined as clinical assessed swollen using a 44 joint assessment.
Lack of ability to understand the information given about the study.
Recent operation in hands or feet (12 month).
Allergy to betamethasone.
Systemic fungal infection
Positive urine HCG among women in the age of fertility.

• Opstart af Disease-modifying anti-rheumatic drugs (DMARD)/biologisk behandling inden for de sidste 12 uger
• Ændring af DMARD/biologisk inden for de seneste 6 uger
• Ændring af glucocorticoid behandlingen inden for de seneste 6 uger
• Opstart af Non-Steroidal Anti-Inflammatory Drugs (NSAID) behandling indenfor de sidste 10 dage
• Kronisk synovit i samme IP-, PIP-, MCP-, hånd-, ankel- og MTP 2-5 led, defineres ved enten svære erosive destruktion, vurderet udfra tidl.
røntgenbilleder eller vedvarende synovit (mdr. 6) ifølge registreringer i DANBIO eller journalen trods led injektion med glucocorticoid mere >1
gang.
• Behandlingskrævende synovit i mere end 4 led, defineret som et klinisk hævet led ved 44 leds vurdering.
• Kontraindikation overfor betamethason, inklusive allergi og systemisk infektion
• Operation i inkluderede led indenfor de sidste 12 uger
• Manglende evne til at forstå informationen om studiet
• Positiv Urin HCG hos kvinder i den fertile alder.

E.5 End points

E.5.1

Primary end point(s)

The primary outcome was the proportion of subjects in each group (A and B) achieving US synovitis remission, defined as US synovitis GS score ≤ 1 and Doppler score = 0, at week 4.

Andelen af deltagere som i hver gruppe (A og B) opnår synovit remission, defineret som UL grey scale score ≤ 1 og colour Doppler score = 0, ved uge 4.

E.5.1.1

Timepoint(s) of evaluation of this end point

After the last visit of the last subject

Efter sidste besøg, af sidste deltager

E.5.2

Secondary end point(s)

The proportion of subjects in each group (A and B) achieving US synovitis remission, defined as US synovitis GS score ≤ 1 and Doppler score = 0, at week 12.

The proportion of subjects in each group (A and B) achieving an acceptable response from the injected joint(s) (binary) at week 4 and 12 weeks.

The proportion of subjects in each group (A and B) achieving clinical joint remission, defined as treated joints with no swollenness and painfulness, at week 4 and 12 weeks.

Differences in the response of synovitis US scores, between treatment arm A and B, at week 4 and 12.

Differences in the response of synovitis US scores ((grey scale, colour Doppler), between treatment arm A and B, at week 4 and 12.

Differences in the response of patient reported Visuel Analog Skala (VAS) local joint pain, for treated joints, between treatment arm A and B, at week 4 and 12.

• Andelen af deltagere som i hver gruppe (A og B) opnår synovit remission, defineret som UL grey scale score ≤ 1 og colour Doppler score = 0, ved uge 12.
• Andelen af deltagere som i hver gruppe (A og B) opnår et acceptabelt respons fra de(t) injicerede led (binært) ved 4 og 12 uger.
• Andelen af deltagere som i hver gruppe (A og B) opnår klinisk vurderet remission, defineret som hverken hævelse eller ømhed af behandlede led, ved uge 4 og 12.
• At sammenligne ændringer af UL synovit scoring (grey scale, colour Doppler), ved 4 og 12 uger, mellem behandlings arm A og B.
• At sammenligne ændringer af patient rapporteret Visuel Analog Skala (VAS) local joint pain for behandlet (de) led, ved uge 4 og 12 mellem behandlings arm A og B.

E.5.2.1

Timepoint(s) of evaluation of this end point

After the last visit of the last subject

Efter sidste besøg, af sidste deltager

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

Yes

E.8.2.3.1

Comparator description

CS in the joint and NaCl Solvens IM vs CS IM and NaCl Solvens in the joint (dobbelt-dummy design)

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

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

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 2017-09-12.

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

Information not present in EudraCT

F.4 Planned number of subjects to be included

F.4.1

In the member state

100

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

2017-11-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-11-02

P. End of Trial
P.	End of Trial Status	Trial now transitioned

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials