Clinical Trials Register

Summary
EudraCT Number:	2019-004139-21
Sponsor's Protocol Code Number:	CTU/2017/306
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2020-03-13
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

UK - MHRA

A.2

EudraCT number

2019-004139-21

A.3

Full title of the trial

A randomised prospective open label pilot trial comparing mycophenolate mofetil (MMF) with no immunosuppression in adults with limited cutaneous systemic sclerosis
MINIMISE-Pilot (Mycophenolate in limited cutaneous systemic sclerosis)

A.3.1

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

Mycophenolate in limited cutaneous systemic sclerosis (MINIMISE-Pilot)

A.3.2

Name or abbreviated title of the trial where available

MINIMISE-Pilot

A.4.1

Sponsor's protocol code number

CTU/2017/306

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 College London
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	Versus Arthritis
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 College London Comprehensive Clinical Trial Unit
B.5.2	Functional name of contact point	Felicia Ikeji
B.5.3	Address:
B.5.3.1	Street Address	2nd Floor, 90 High Holborn
B.5.3.2	Town/ city	London
B.5.3.3	Post code	WC1V 6LJ
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	020 7679 9506
B.5.6	E-mail	cctu.minimise@ucl.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	Mycophenolate Mofetil
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord Healthcare Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Mycophenolate Mofetil
D.3.2	Product code	MMF
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Mycophenolate mofetil
D.3.9.1	CAS number	24280-93-1
D.3.9.4	EV Substance Code	AS1
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	500
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Limited cutaneous systemic sclerosis (lcSSc)

E.1.1.1

Medical condition in easily understood language

Scleroderma

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10042953
E.1.2	Term	Systemic sclerosis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10011380
E.1.2	Term	CREST syndrome
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to assess recruitment feasibility and to assess whether patients with limited cutaneous systemic sclerosis (lcSSc) on mycophenolate mofetil (MMF) have a lower rate of development of important complications that reflect "clinical worsening" than patients not on immunosuppression. Feasibility and clinical outcomes will be measured.
This will inform the development of a future larger trial that could potentially transform lcSSc patient management.

Feasibility outcomes will measure:

• Recruitment rate (the proportion of eligible participants enrolled
into the trial)
• Adherence to the protocol (by participants and clinicians/research
teams at sites)
• Proportion of participants intolerant to MMF who discontinue therapy
• Proportion of MMF participants who reduce their dose
• Proportion of MMF tablets taken
• Loss to follow up in each group (MMF and Control)
• Informat

E.2.2

Secondary objectives of the trial

1.Safety and tolerability determined by the number and type of the following occurring in the trial:
•Adverse events
•Serious adverse events
•Serious adverse reactions

2.Frequency of each of the components of the composite primary endpoints

3.Change in quality of life and symptom scores:
• Modified Rodnan skin score
• Quality of life and functional ability - Assessed by Scleroderma Health
Assessment Questionnaire
• Health related quality of life - Assessed by EQ5-5D-5L Questionnaire
• Pain and disability - Assessed by Patient Global Assessment
• Pain and disability - Assessed by Physician's global assessment

4.Subgroup analysis by:
• ANA pattern (Antinuclear antibodies): ACA+ versus ACA-
• Disease duration at baseline: up to 4 years versus four years or more

E.2.3

Trial contains a sub-study

E.2.3.1

Full title, date and version of each sub-study and their related objectives

1. Capillaroscopic sub-study (included in main protocol): aims to explore whether defined abnormalities of the small blood vessels in the fingers can predict the time to development of complications of limited cutaneous systemic sclerosis.

2. Skin Biopsy sub-study: aims to analyse how gene expression subset predicts different outcome in limited cutaneous systemic sclerosis patients receiving mycophenolate mofetil (MMF) and those on standard of care alone. Recent gene expression analysis in limited cutaneous systemic sclerosis patients have demonstrated that patients can be separated into two major groups, "limited 1" and "limited 2", and each group present different disease outcomes.

E.3

Principal inclusion criteria

1.Confirmed diagnosis of limited cutaneous subset of systemic sclerosis
2.Participants with less than 7 years disease duration from first non-Raynaud's manifestation of systemic sclerosis
3.Participants aged 18 years or more (≥ 18 years) at screening visit
4.Female participant not pregnant or breast feeding
5.Negative viral screen for HIV, Hepatitis B and C, and VZV Ig
6.Ability to provide full informed consent
7.Registered with a GP practice in the UK
8.Participants must be willing to attend for follow up visits and to comply with study-related procedures

E.4

Principal exclusion criteria

1.Having already developed a complication of SSc that requires initiation of MMF or an alternative major immunosuppressive drug for SSc such as methotrexate, cyclophosphamide or azathioprine
2.Treatment with methotrexate, cyclosporine A, azathioprine, mycophenolate mofetil (MMF), rapamycin, colchicine, D-penicillamine, within ≤ 4 weeks prior to the baseline visit date
3.Contraindication to MMF or previous intolerance of MMF
4.Any clinical condition which the investigator considers would make the participant unsuitable for the trial
5.Pregnancy (or planned pregnancy during trial participation) and/or breastfeeding
6.Female participants and male participants with a partner of child bearing potential not willing to use adequate contraception
7.Active chronic infection such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria
8.Infection history
i.Hospitalisation for treatment of infection within ≤ 8 weeks of screening visit date
ii.Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within ≤ 4 weeks of screening visit date
9.Receipt of a live-attenuated vaccine within ≤ 12 weeks of screening visit date
10.Participants enrolled in any other interventional trial within ≤ 4 weeks of the screening visit date (co-enrolment in observational studies is acceptable)
11.Current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within ≤ 52 weeks prior to screening visit date.

E.5 End points

E.5.1

Primary end point(s)

The primary objective of this pilot trial is to assess recruitment feasibility and endpoint viability for an event-driven trial. This external pilot trial will inform the design of a definitive double-blind placebo-controlled trial.

The primary outcomes are:

Feasibility outcomes

• Recruitment rate (the proportion of eligible patients enrolled into the trial)
Through the use of a detailed screening logs we will obtain information on the total number of lcSSc patients screened, the proportion of patients who meet eligibility criteria and the proportion of eligible patients who provide consent and thus are enrolled into the trial.
• Adherence to the study protocol (by participants and clinicians/research teams at sites)
 proportion of participants intolerant to MMF who discontinue therapy
 proportion of MMF participants who reduce their dose
 proportion of MMF tablets taken
 loss to follow up in each group (MMF and Control)

• Information to guide the design of the definitive double-blind placebo-controlled trial by providing data to:
o Estimate the number of centres and the length of the recruitment
period that will be required for the definitive double-blind
placebo-controlled trial
o Identify any barriers to recruitment
o Assess the rate of withdrawal from treatment due to adverse events
and the rate of loss to follow up
• Information to guide the design of the economic evaluation of the definitive double-blind placebo-controlled trial

Clinical outcomes

• Time to clinical worsening of lcSSc defined as development of new clinically significant endpoint such as:

o Progressive lung fibrosis
o Pulmonary hypertension
o Scleroderma renal crisis
o Heart failure
o Severe gut involvement causing malnutrition
o Major vascular complications in the fingers such as gangrene
o Mortality

E.5.1.1

Timepoint(s) of evaluation of this end point

Between baseline and up to Week 96.

E.5.2

Secondary end point(s)

1.Safety and tolerability determined by the number and type of adverse events, serious adverse events and serious adverse reactions occurring in the trial

2.Frequency of each of the components of the composite primary endpoints

3.Change in the quality of life and symptom scores:
o Modified Rodnan skin score
o Quality of life and functional ability - Assessed by Scleroderma
Health Assessment Questionnaire (SHAQ)
o Health related quality of life - Assessed by EQ5-5D-5L Questionnaire
o Pain and disability - Assessed by Patient Global Assessment
o Pain and disability - Assessed by Physician's global assessment

4.Subgroup analysis by:
o ANA (autoantibodies) pattern: ACA+ versus ACA-
o Disease duration at baseline: up to 4 years versus four years or more

E.5.2.1

Timepoint(s) of evaluation of this end point

Between baseline and up to Week 96.

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

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

Feasibility

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Yes

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

Yes

E.8.1.7.1

Other trial design description

Randomised prospective open label

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

Yes

E.8.2.3.1

Comparator description

Standard of care

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

The end of trial will be defined as the date when all outstanding data queries have been resolved following the last participant’s 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