Clinical Trials Register

Summary
EudraCT Number:	2012-002640-25
Sponsor's Protocol Code Number:	RR12/10234
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-01-07
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

UK - MHRA

A.2

EudraCT number

2012-002640-25

A.3

Full title of the trial

A prospective, single-centre, feasibility study evaluating the prevalence of diagnostic clinical imaging features of subclinical enthesitis in patients with moderate to severe plaque psoriasis and the response to skin directed treatment with Ustekinumab

A.3.1

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

Detecting early pre-symptomatic psoriatic arthritis in patients with skin moderate or severe psoriasis - how effective is ustekinumab (Stelara) in limiting joint disease progression and future disability?

A.3.2

Name or abbreviated title of the trial where available

MUSTEK Study (Protocol Version 1.0)

A.4.1

Sponsor's protocol code number

RR12/10234

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN18043449

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 of Leeds/Leeds Teaching Hospitals NHS Trust
B.1.3.4	Country	United Kingdom
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	Leeds Foundation for Dermatology Research
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	Janssen-Cilag (Pharmaceuticals) Ltd.
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University of Leeds Institute of Molecular Medicine (Section of Musculoskeletal Disease)
B.5.2	Functional name of contact point	Academic Unit of MSK Disease
B.5.3	Address:
B.5.3.1	Street Address	Level 2, Chapel Allerton Hospital, Chapeltown Road,
B.5.3.2	Town/ city	Leeds
B.5.3.3	Post code	LS7 4SA
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	07817407699
B.5.5	Fax number	01133924650
B.5.6	E-mail	D.G.McGonagle@leeds.ac.uk

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	Stelara
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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	Ustekinumab
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ustekinumab
D.3.9.1	CAS number	815610-63-0
D.3.9.4	EV Substance Code	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	90
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Psoriatic disease (psoriasis and psoriatic arthritis).

E.1.1.1

Medical condition in easily understood language

Skin psoriasis and the related bone, joint and soft tissue changes associated with psoriasis (psoriatic arthritis).

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10066579
E.1.2	Term	Progression of psoriatic arthritis
E.1.2	System Organ Class	100000004859

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10071117
E.1.2	Term	Plaque psoriasis
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10037160
E.1.2	Term	Psoriatic arthritis
E.1.2	System Organ Class	100000004859

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10050576
E.1.2	Term	Psoriasis vulgaris
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10037153
E.1.2	Term	Psoriasis
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10037157
E.1.2	Term	Psoriasis of scalp
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10063407
E.1.2	Term	Psoriasis genital
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10028703
E.1.2	Term	Nail psoriasis
E.1.2	System Organ Class	10040785 - Skin and subcutaneous 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

Do the imaging features of subclinical enthesopathy (the earliest change seen in psoriatic arthritis), as measured by peripheral joint ultrasound (USS) and whole body MRI, in patients with moderate-to-severe psoriasis (PASI>10), change when treated for 24 weeks with ustekinumab (at standard dose) for their psoriatic skin disease?

E.2.2

Secondary objectives of the trial

a. To estimate the baseline prevalence of peripheral subclinical enthesitis (on ulrasound and MRI) in systemic and biologic treatment-naïve patients with plaque psoriasis, recruited from a new-patient psoriasis clinic, with a PASI score greater than 10 and no symptoms of joint disease (as assessed by the CASPAR criteria) at presentation. b. To estimate the baseline prevalence of subclinical axial arthropathy on magnetic resonance imaging in systemic and biologic treatment-naïve patients with plaque psoriasis, recruited from a new-patient psoriasis clinic, with a PASI score greater than 10 and no symptoms of joint disease (as assessed by the CASPAR criteria) at presentation. c. To assess the change in MRI parameters of subclinical peripheral and axial inflammatory joint disease from baseline in patients with psoriasis treated for 24 weeks with ustekinumab for their skin disease d. To establish if a relationship exists between the change from baseline in any routine clinical s

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

The additional serological samples taken as part of the sub study all come under the umbrella of 'Bioscreening, marker discovery and DNA extraction in psoriatic disease'. They relate to the main study by adding a further dimension to concept of identifying early psoriatic arthritis (biological and genetic markers), in addition to adding further to the overall understanding of psoriasis pathogenesis. Ethical approval has been granted for work to be carried out into the 'Significance of the interplay between danger/damage associated molecules (DAMPs) and the cytokine network for the outcome of inflammatory skin diseases (including psoriasis)' (REC reference 11/YH/0368. (Protocol Version 2.0, dated 5.10.11). Any further research will be subject to a new ethics submission and approval.

E.3

Principal inclusion criteria

1. Male and female patients aged from 18 to 80 years (inclusive) 2. A clinical diagnosis of chronic plaque psoriasis 3. Duration of psoriasis greater than twelve months 4. Moderate or severe skin disease (classified as a PASI score >10) 5. No prior treatment with systemic or biologic agents 6. No current or prior symptoms of psoriatic arthritis (or arthralgia/articular symptoms) 7. A physical ability to undergo USS, OCT and MRI scanning 8. An ability to permit the administration of subcutaneous medication by Dr Laura Savage (PI). 9. All male and female subjects biologically capable of having children must agree to use at least one reliable method of contraception for the duration of the study and for 24 weeks after the end of the study. Acceptable methods of contraception are surgical sterilization, oral, implantable or injectable hormonal methods, intrauterine devices or barrier contraceptives

E.4

Principal exclusion criteria

1. Male and female patients aged 17 and under or 81 and over (inclusive) 2. Psoriasis of mild to moderate psoriasis (PASI<10) 3. Previous treatment with any systemic or biologic agents (for psoriasis or any other indication) 4. Patients unable or not willing to attend all imaging, serological and clinical assessments 5. Any contraindication to MRI scanning (e.g. pacemaker, aneurysm coil) 6. Patients not willing to use adequate contraceptive methods 7. Pregnancy or breast feeding 8. Any contraindication to biologic therapy: o Active infection, including open leg ulcers, HIV, hepatitis B or C carriers o Active or latent tuberculosis o Malignancy – current, or previous within the last ten years (except basal cell carcinoma) o Severe heart failure (NYHA grade 3 or more) o Demyelinating disorders o Uncontrolled diabetes o Chronic lung disease (pulmonary fibrosis or bronchiectasis) o Previous PUVA phototherapy (>1000 joules) 9. History of other significant medical conditions, including: o Severe pulmonary disease (defined as requiring previous hospital admission or supplemental oxygen) o Active or severe cardiovascular disorders: uncontrolled hypertension, myocardial infarction within the previous twelve months, unstable angina within the previous six months) o Any immunodeficiency disorder o Connective tissue diseases (e.g. primary Sjogrens syndrome, systemic sclerosis, systemic lupus erythematosus, polymyositis) o Renal impairment (creatinine clearance <45ml/min) o Abnormal liver function tests (alanine transferase >3x upper limit of normal) o Blood disorders, i.e. neutropenia (neutrophils <2.0x109/l), thrombocytopenia (platelets <125x109/l) or anaemia (haemoglobin <8g/dl). 10. Any forthcoming event that may interrupt participation (e.g. a holiday, elective hospital admission) lasting longer than 14 days. Whilst some of the above are absolute contraindications, physician discretion will be applied as in usual clinical practice.

E.5 End points

E.5.1

Primary end point(s)

The change in enthesopathy measurements (total modified GUESS score - calculated from high resolution GS and PD ultrasound assessment of the upper and lower limb entheses) from baseline following 12 then 24 weeks of treatment with ustekinumab (open-label), prescribed to treat moderate or severe chronic plaque psoriasis.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 0 (baseline), week 12 and week 24.

E.5.2

Secondary end point(s)

1. PASI, DLQI and NAPSI Scores 2. BSA quantification (%) 3. MRI assessment of axial and peripheral features of early PsA (e.g. enthesopathy, dactylitis, bone oedema etc.) 4. OCT assessment of the fingernails 5. USS assessment of the fingernails 6. FBC, U&E, LFT, CRP, PV, ANA, HDL and LDL cholesterol, triglycerides, glucose, hs-CRP, adiponectin, resistin

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 0 (baseline), week 12 and week 24 for all endpoints except MRI (week 0 and 24 only).

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

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

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.8.4.1

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

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 (last visit, last subject)

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