Clinical Trials Register

Summary
EudraCT Number:	2016-002578-11
Sponsor's Protocol Code Number:	917741
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:	2016-08-09
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

2016-002578-11

A.3

Full title of the trial

The cystic fibrosis (CF) anti-staphylococcal antibiotic prophylaxis trial (CF START); a randomised registry trial to assess the safety and efficacy of flucloxacillin as a longterm prophylaxis agent for infants with CF.

A.3.1

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

A trial to determine the safest and most effective antibiotic strategy for infants diagnosed with CF.

A.3.2

Name or abbreviated title of the trial where available

CF START

A.4.1

Sponsor's protocol code number

917741

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	Alder Hey Children's 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 (HTA, 14/22/23)
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	MC- CTU
B.5.2	Functional name of contact point	Abigail Bennett
B.5.3	Address:
B.5.3.1	Street Address	CTRC, MC-CTU (University of Liverpool), Institute of Child Health, Alder Hey Children's NHS FT
B.5.3.2	Town/ city	Liverpool
B.5.3.3	Post code	L12 2AP
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00 44 (0) 151 794 9764
B.5.5	Fax number	00 44 (0) 151 282 4721
B.5.6	E-mail	cfstart@liverpool.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	Information not present in EudraCT
D.2.1.1.1	Trade name	Flucloxacillin 250mg/5ml Sugar-Free Powder for Oral Solution
D.2.1.1.2	Name of the Marketing Authorisation holder	Actavis Group PTC ehf
D.2.1.2	Country which granted the Marketing Authorisation	Iceland
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	Flucloxacillin
D.3.2	Product code	na
D.3.4	Pharmaceutical form	Powder for oral solution
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	Flucloxacillin
D.3.9.1	CAS number	5250-39-5
D.3.9.4	EV Substance Code	AS1
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	25-50 to mg/ml
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

Cystic fibrosis

E.1.1.1

Medical condition in easily understood language

A life-limiting inherited condition caused by a faulty gene that controls the movement of salt and water in and out of cells. Causing mucus to gather in the lungs and digestive system.

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10011762
E.1.2	Term	Cystic fibrosis
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic 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

To demonstrate that infants on anti-staphylococcal antibiotic prophylaxis (“Prevent and Treat”) are not predisposed to earlier airway infection with Pseudomonas aeruginosa.

E.2.2

Secondary objectives of the trial

- To determine if anti-staphylococcal antibiotic prophylaxis (ASAP) improves respiratory function in pre-school children with CF
- To determine the need for extra antibiotic treatment
- To determine the number and type of respiratory culture taken during the trial period
- To determine the number and proportion of respiratory cultures positive for Staphylococcus aureus (SA)
- To determine the number and proportion of respiratory cultures positive for Pseudomonas aeruginosa (PsA)
- To determine the number and proportion of respiratory cultures positive for other significant CF pathogens
- To determine if there is evidence of chronic airway infection
- To determine the frequency of hospital admission
- To identify any adverse events
- To determine nutritional status
- To determine the costs to the NHS

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. A confirmed diagnosis of cystic fibrosis through one of the following three routes:
- Two CF-causing mutations are identified.
OR
- One or no CF- causing mutations identified and a sweat chloride test result greater than 59 mmol/L.
OR
- Two CFTR mutations (not known CF-causing mutations) and a sweat chloride test result greater than 29 mmol/L.
2. Age 70 days or less.
3. Consent for inclusion on the national UK CF Registry.
4. Consent for inclusion in the CF START trial.

E.4

Principal exclusion criteria

1. An inconclusive diagnosis after newborn screening (NBS).*
2. A condition (non-CF) that, in the opinion of the recruiting investigator will impact on the long-term management and outcome of a participant with CF.**
3. Previous growth of PsA from respiratory culture.
4. Infants with a history of hypersensitivity to β-lactam antibiotics (e.g. penicillins) or excipients
5. Infants with a history of flucloxacillin associated jaundice/hepatic dysfunction.

*Infants with an inconclusive diagnosis after NBS (termed ‘CF Screen Positive Inconclusive Diagnosis (CFSPID)’) should not receive standard CF care and should not be recruited into CF START (Munck et al 2015).
The two situations that result in a diagnosis of CFSPID after NBS are;
• Two CFTR mutations recognised, one or both of which are not characterised as CF-causing and the sweat chloride is less than 30 mmol/L
• The sweat chloride is repeatedly between 30-59 mmol/L and only one or no CFTR mutations are recognised

**Significant non-CF conditions might include chromosomal abnormality (for example, Down syndrome), cerebral palsy, chronic lung disease (oxygen requirement) following pre-term birth and other significant congenital anomalies (for example, severe cardiac disease, tracheo-oesophageal fistula, diaphragmatic hernia).

E.5 End points

E.5.1

Primary end point(s)

Age at first growth of Pseudomonas aeruginosa from respiratory culture collected as part of routine care

E.5.1.1

Timepoint(s) of evaluation of this end point

All routine clinical encounters to trial completion (age, 48 months)

E.5.2

Secondary end point(s)

To determine the need for extra antibiotic treatment
To determine the number and type of respiratory culture taken during the trial period
To determine the number and proportion of respiratory cultures positive for Staphylococcus aureus (SA)
To determine the number and proportion of respiratory cultures positive for Pseudomonas aeruginosa (PsA)
To determine the number and proportion of respiratory cultures positive for other significant CF pathogens
To determine if there is evidence of chronic airway infection
To determine the frequency of hospital admission
To identify any adverse events
To determine nutritional status
To determine the costs to the NHS

E.5.2.1

Timepoint(s) of evaluation of this end point

All secondary endpoints detailed above will be recorded at all encounters to trial completion (age, 48 months). Apart from determining if ASAP improves respiratory function in pre-school children with CF which will be evaluated at trial visits between the age of 40-48 months. As well as determining nutritional status which will be evaluated at encounters between 40-48 months.

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

Yes

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

Yes

E.8.1.3

Single blind

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Antibiotics given in a targeted manner as per national guidelines

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

130

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 is defined to be the date on which data for all participants is frozen and data entry privileges are withdrawn from the trial database.

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

Yes

F.1.1