Clinical Trials Register

Summary
EudraCT Number:	2019-001618-41
Sponsor's Protocol Code Number:	FERARO
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:	2020-03-02
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

2019-001618-41

A.3

Full title of the trial

FERARO: A prospective, randomised placebo controlled feasibility trial of Faecal microbiota Transplant to ERadicate gastrointestinal carriage of Antibiotic Resistant Organisms

A.3.1

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

Can restoring the balance of healthy bowel bacteria help to fight antibiotic resistant bugs?

A.3.2

Name or abbreviated title of the trial where available

FERARO

A.4.1

Sponsor's protocol code number

FERARO

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	Guy's and St Thomas NHS Foundation 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	NIHR
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	Guy's and St Thomas' NHS Foundation Trust
B.5.2	Functional name of contact point	Simon Goldenberg
B.5.3	Address:
B.5.3.1	Street Address	Directorate of Infection 5th Floor North Wing St Thomas’ Hospital Westminster Bridge Road London
B.5.3.2	Town/ city	London
B.5.3.3	Post code	SE1 7EH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	0207 188 8515
B.5.6	E-mail	simon.goldenberg@gstt.nhs.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	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	Faecal Microbiota for Transplantation
D.3.4	Pharmaceutical form	Capsule, hard
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	Faecal Microbiota
D.3.9.3	Other descriptive name	Faecal Microbiota
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	240
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)	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

Gastrointestinal colonisation and infection with Extended Spectrum Beta-lactamase (ESBL) producing Enetrobacteriales and Carbapenemase Producing Enetrobacteriales

E.1.1.1

Medical condition in easily understood language

Antibiotic resistant bacteria

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

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	10004052
E.1.2	Term	Bacterial resistance
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10034133
E.1.2	Term	Pathogen resistance
E.1.2	System Organ Class	10021881 - Infections and infestations

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 primary objective is to determine the feasibility of administering capsulised FMT to participants with the eventual aim of eliminating or reducing stool carriage of MDRGNO as detected by stool culture and PCR for up to 6 months after end of therapy.

E.2.2

Secondary objectives of the trial

Feasibility
The study will continue to measure how feasible it is to conduct a clinical trial of FMT treatment, by measuring the following:

- no. of patients meeting the eligibility criteria for the study
- no. of patients receiving the treatment
- no.of patients returning for follow up appointments
- no.of patients providing stool samples

The ability to recruit enough healthy donors to manufacture the FMT needed for the trial will also be measured.

Efficacy
The presence of ARB in stool samples provided by patients after receiving FMT or placebo will be measured to see if FMT reduces the amount of bugs in the gut.

Safety and Tolerability
The proportion of patients experiencing side effects, and any adverse events will be measured.

The secondary objectives will provide the evidence needed to determine how to measure if the treatment works (the primary outcome) in a larger clinical trial, and the number of people needed to take part.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Participant / patient Inclusion criteria

• Adult patients (age >18 years or older at time of randomisationconsent)
• Current or previous patient at Guy’s and St Thomas’ NHS Foundation Trust
• Ability to understand the purpose, potential benefits and risks of the study and capable of giving informed consent. The participant must be able to provide written informed consent.
• Documented gastrointestinal carriage of ESBL or CPE (stool sample) in the 21 days prior to consent.
• Symptomatic infection with the same target organism of interest in the preceding 6 months

Donor Inclusion criteria

• Aged between 18 and 60 years of age
• Body mass index between 18 and 30

E.4

Principal exclusion criteria

Participant / patient Exclusion criteria

• Pregnancy or planned pregnancy. Urine testing will be performed at randomisation to rule out pregnancy in females.
• Breastfeeding
• Severe or life-threatening food allergy
• Allergy or other contraindication to omeprazole, IMP or placebo ingredients
• Treatment with systemic antibiotic on the day of and day prior to 1st IMP/placebo dosing to the end of the dosing period
• Treatment with pre or probiotics in the 4 weeks prior to randomisation and for the duration of the study.*
• Severe immunodeficiency;
o systemic chemotherapy <30 days from baseline or planned chemotherapy within the upcoming 6 months
o Known HIV infection with CD4 count <250 cells/uL
o Known neutropenia with absolute neutrophils <1.0x109
o Prolonged treatment with corticosteroids (equivalent to prednisone >60mg daily for > 30 days) within 8 weeks of randomisation
• Life expectancy <6 months
• Swallowing disorder, oral-motor dyscoordination or likely inability/unwillingness to ingest study medication
• Patients who have received another investigational drug or device within 4 months prior to randomisation

* There are no universally accepted definitions of pre and probiotics, and there are a plethora of products available. These substances are often contained in several commonly consumed foodstuffs e.g. yoghurt, cheese, beer etc. For the purposes of this study patients who consume foodstuffs containing pre and probiotics will not be excluded from the trial, other products will be reviewed on a case by case basis. A rule of thumb to aid decision making is to allow products that can be found in the food aisles of supermarkets and exclude products that can found in the pharmacy/health products or vitamins aisle.

Donor Exclusion criteria

• Not have received any antimicrobials within the past 3 months
• Not have any known prior exposure to HIV and/or viral hepatitis, and known previous or latent tuberculosis
• Not have any risk factors for blood borne viruses, including high risk sexual behaviours, use of illicit drugs, any tattoo/body piercing/needlestick injury/blood transfusion/acupuncture, all within the previous 6 months
• Signs or symptoms consistent with Covid-19 / a nose/throat and/or stool sample with detectable SARS-CoV-2
• Not received a live attenuated vaccine within the past 6 months
• Not have any underlying gastrointestinal conditions/symptoms (e.g., history of IBD, irritable bowel syndrome (IBS), chronic diarrhoea, chronic constipation, coeliac disease, bowel resection or bariatric surgery),
• Not have also any acute diarrhoea/gastrointestinal symptoms within the 2 weeks prior to donating
• Not have any family history of any significant gastrointestinal conditions (e.g., family history of Inflammatory Bowel Disease (IBD) or colorectal cancer)
• Not have any history of atopy (e.g., asthma, eosinophilic disorders)
• Not have any systemic autoimmune conditions
• Not have any metabolic conditions, including diabetes and obesity
• Not have any neurological or psychiatric conditions, or known risk of prion disease
• Not have any history of chronic pain syndromes, including chronic fatigue syndrome and fibromyalgia
• No have any history of any malignancy
• Not currently taking any regular medications
• No history of taking the following medications within the past 3 months; proton pump inhibitors, immunosuppression, chemotherapy.
• No history of receiving growth hormone, insulin from cows or clotting factor concentrates.
• No history of receiving an experimental medicine or vaccine within the past 6 months
• No history of travel to tropical countries within the past 6 months

E.5 End points

E.5.1

Primary end point(s)

The primary outcome is the consent rate (as a proportion of participants who fulfil inclusion / exclusion criteria). This will be used to determine if a substantive trial is feasible.

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary outcome is a composite measure which can only be assessed once all patients have had the opportunity to participate, and thus will only be measured at the end of the trial.

E.5.2

Secondary end point(s)

The secondary endpoints of the study are to provide preliminary evidence of efficacy for a substantive randomised controlled trial with the purpose of
choosing the optimal primary outcome estimating the parameters for sample size calculation

Secondary outcomes of feasibility are;
Proportion of patients fulfilling inclusion / exclusion criteria
Proportion of patients receiving IMP / placebo (as a % of those consenting)
Proportion of patients returning for follow up visits (face to face visit at Day 40)
Proportion of patients providing follow up stool samples (Days)
Ability to recruit sufficient healthy donors to manufacture all FMT doses to meet demands of this and a future substantive RCT. Assessed by delay in dosing patients (measured in days)

Additional feasibility assessments will include:

Collection of data that may be used in estimating of costs/resources needed to provide FMT in the NHS.
An embedded qualitative study to explore views and experiences of research participants.

Secondary outcomes of efficacy are;
Gastrointestinal carriage of CRE / ESBL (detected / not detected) by stool culture over time (days 10, 40, 100 and 190)
Gastrointestinal carriage of CRE / ESBL (detected / not detected) by multiplex PCR over time (days 10, 40, 100 and 190)

Secondary outcomes of safety and tolerability are;
proportion of patients experiencing reflux following administration of FMT
Proportion of patients suffering intolerable (resulting in withdrawal from the study) gastrointestinal side effects (including diarrhoea, constipation, abdominal pain, flatulence and bloating). This will be assessed by direct questioning and completion of a short patient questionnaire.
identification of unanticipated harms involved with administration of FMT.
occurrence of any adverse event / serious adverse event

E.5.2.1

Timepoint(s) of evaluation of this end point

Feasibility assessments will be evaluated at end of trial (additional assessments at month 6 and 12) with the exception of the qualitative study which will be performed during months 6 to 12 of the study.

Safety and tolerability assessments will be assessed for each patient following each dosing day (days 1, 2 and 3) and all follow up timepoints (days 10, 40, 100 and 190) as well as any unscheduled participant visits.

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)

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

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

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

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

The end of the trial will be defined as database lock.

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