Clinical Trials Register

Summary
EudraCT Number:	2015-000963-15
Sponsor's Protocol Code Number:	MATCH0.1
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:	2015-12-02
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

UK - MHRA

A.2

EudraCT number

2015-000963-15

A.3

Full title of the trial

MAcrophage Therapy for Liver Cirrhosis (MATCH)

A.3.1

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

MATCH

A.3.2

Name or abbreviated title of the trial where available

MAcrophage Therapy for Liver Cirrhosis (MATCH)

A.4.1

Sponsor's protocol code number

MATCH0.1

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN10368050

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 Edinburgh
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	MRC
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 Edinburgh
B.5.2	Functional name of contact point	Professor Stuart Forbes
B.5.3	Address:
B.5.3.1	Street Address	5 Little France Drive
B.5.3.2	Town/ city	Edinburgh
B.5.3.3	Post code	EH16 4UU
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	0131 651 9500
B.5.6	E-mail	stuart.forbes@ed.ac.uk
B.Sponsor: 2
B.1.1	Name of Sponsor	NHS Lothian
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	No
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	Autologous Macrophage Cell Product
D.3.2	Product code	MATCH
D.3.4	Pharmaceutical form	Dispersion for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.2	Concentration type	up to
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	Yes
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

Liver Cirrhosis

E.1.1.1

Medical condition in easily understood language

Liver disease causing scarring of the liver

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10024667
E.1.2	Term	Liver cirrhosis
E.1.2	System Organ Class	100000004871

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Phase I (dose escalation study):
The primary objective of this study is to demonstrate safety and the maximum tolerated dose of autologous monocyte derived macrophages in participants with advanced liver cirrhosis.

Phase II (repeat dosing study):
The primary objective of the repeat dosing study is to demonstrate an improvement in the severity of liver disease over 3 months.

E.2.2

Secondary objectives of the trial

Secondary objectives are to demonstrate improvement in markers of liver fibrosis, improved disease related quality of life, reduced liver related clinical events and improved transplant free survival.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

INCLUSION CRITERIA

1. 18≥ AGE ≤75 at screening

2. Aetiology: one or more of:

• Alcohol Related Liver Disease (ALD)
No active alcohol misuse ≥6 calendar months prior to screening. Features of chronic liver disease with a compatible history of alcohol excess (>80g/day), in the absence of other causes of chronic liver disease. Participants with other aetiologies of liver disease may drink alcohol within current recommended limits (14 units per week for females and for males)

• Primary Biliary Cirrhosis (PBC)
2 out of:
Cholestatic LFTs
Positive AMA (>1:40)
Compatible Histology

If already receiving Ursodeoxycholic Acid must be established on current dose >3 months prior to enrolment

• Non-Alcoholic Fatty Liver Disease (NAFLD)

Either:
Histological evidence of steatosis in the absence of other liver diseases
Or:
Imaging compatible with NAFLD (eg Fatty infiltration of liver) and one or more risk factors (e.g. elevated BMI, T2DM, Hypertriglyceridaemia, Hypertension)
And:

The absence of significant alcohol consumption (<20g/day) and no evidence of other causes of chronic liver disease

• Cryptogenic cirrhosis

Diagnosis of cirrhosis unattributable to any other cause

• Haemochromatosis

Diagnosis made on basis of compatible Biochemistry (Transferrin Sat >60%, Ferritin >400), Genotype (Homozygous C282Y or H63D, Compound Heterozygote) or Histology

• Alpha-1 anti-trypsin deficiency

Diagnosis based on compatible genetic, phenotypic or histological testing.

• Previous Hepatitis C (sustained viral response ie. undetectable HCV RNA 24 weeks after completion of treatment.)

3. Diagnosis of Cirrhosis – invasive or non-invasive;

Cirrhosis, defined as one of:

• Previous liver biopsy confirming histological features of cirrhosis

• Transient Elastography (Fibroscan) >15 kPa

• Clinical and radiological features that in the opinion of the investigator correlate with a diagnosis of cirrhosis

4. 10>/MELD score</17 at screening

E.4

Principal exclusion criteria

EXCLUSION CRITERIA

• Refusal or inability to give informed consent to participate in the study

• Other cause of chronic liver disease / cirrhosis not included in listed aetiologies – this is left to the clinical judgement of the investigator based on previous investigations and trial screening

• Portal Hypertensive Bleeding; active episode of bleeding requiring hospitalisation in the last 3 months

• Ascites unless, in the opinion of the investigator, the ascites is minimal and well controlled with no increase to diuretic therapy in last 3 months

• Encephalopathy; current or requiring hospitalisation for treatment in last 3 months

• Hepatocellular Carcinoma – uncertain cases to be discussed at local hepatobiliary Multidisciplinary meeting, dysplastic or indeterminate nodules to be excluded, regenerative or other nodules to be included at discretion of MDM

• Previous diagnosis of Hepatocellular Carcinoma

• Previous organ Transplant or previous recipient of tissue

• Listed for Liver Transplantation

• Any situation that in the Investigators opinion may interfere with optimal study participation such as alcohol or drug abuse, domicile too distant from study site, potential non-compliance or inability to co-operate

• Presence of clinically relevant acute illness that in the opinion of the investigator might compromise the participant’s safe participation in the study

• Presence or history of cancer within past 5 years with exception of adequately treated localised skin carcinoma, in situ cervical cancer or solid malignancy surgically excised in total without recurrence for 5 years

• Pregnancy or Breastfeeding

• Allergy to steroids

- Active infection on the mandatory microbiology blood tests
- Immunosuppressants eg Azathioprine
- Current enrolment in an interventional study

E.5 End points

E.5.1

Primary end point(s)

Phase I (dose escalation study)
The primary endpoints are the safety and feasibility and to establish the maximum safe dose of infusion of autologous macrophages to cirrhotic participants

Phase II (repeat dosing study)
The change in MELD (Model for End Stage Liver Disease) score (delta MELD) at 3 months from the 1st infusion of macrophages

E.5.1.1

Timepoint(s) of evaluation of this end point

phase I endpoint once all patients in dose escalation have completed all treatment and reached 14 days safety visit. all patients will be monitored for 1 year post infusion
phase II endpoint 3 months post infusion

E.5.2

Secondary end point(s)

Secondary endpoints are changes in the ELF (Enhanced Liver Fibrosis) panel, Protein Fingerprint Biomarkers, Fibroscan, Chronic Liver Disease Quality of Life, UKELD (United Kingdom Model for End Stage Liver disease), blood parameters, number of clinical events and transplant free survival

E.5.2.1

Timepoint(s) of evaluation of this end point

base line to 90 days changes in our secondary endpoint measures, all patients will be monitored for 1 year post infusion

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)

Yes

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

The latter RCT phase is powered to assess efficacy

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

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 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 study is defined as 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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1