Clinical Trials Register

Summary
EudraCT Number:	2012-003476-39
Sponsor's Protocol Code Number:	RG_12-188
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:	2012-11-30
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

2012-003476-39

A.3

Full title of the trial

Short course daily prednisolone therapy at the time of upper respiratory tract infection in children with relapsing steroid sensitive nephrotic syndrome; the PREDNOS 2 study.

A.3.1

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

Short course daily prednisolone therapy at the time of upper respiratory tract infection in children with relapsing steroid sensitive nephrotic syndrome; the PREDNOS 2 study.

A.3.2

Name or abbreviated title of the trial where available

PREDNOS 2

A.4.1

Sponsor's protocol code number

RG_12-188

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN10900733

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	The University of Birmingham
B.1.3.4	Country
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
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 Birmingham
B.5.2	Functional name of contact point	Elizabeth Brettell
B.5.3	Address:
B.5.3.1	Street Address	BCTU, College of Medical and Dental Sciences
B.5.3.2	Town/ city	Edgbaston, Birmingham
B.5.3.3	Post code	B15 2TT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01214159130
B.5.5	Fax number	01214159135
B.5.6	E-mail	E.A.Brettell@bham.ac.uk
B.Sponsor: 2
B.1.1	Name of Sponsor	Manchester University 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
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 Birmingham
B.5.2	Functional name of contact point	Elizabeth Brettell
B.5.3	Address:
B.5.3.1	Street Address	Birmingham Clinical Trials Unit
B.5.3.2	Town/ city	Edgbaston, Birmingham
B.5.3.3	Post code	B15 2TT
B.5.4	Telephone number	01214159130
B.5.5	Fax number	01214159135
B.5.6	E-mail	e.a.brettell@bham.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	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	Prednisolone
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	Prednisolone
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	5
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
D.8.3	Pharmaceutical form of the placebo	Tablet
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

Relapsing steroid sensitive nephrotic syndrome

E.1.1.1

Medical condition in easily understood language

Relapsing steroid sensitive nephrotic syndrome

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

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 determine whether a six day course of oral prednisolone given at the time of URTI reduces the incidence of first URTI-related relapse in children with relapsing steroid sensitive nephrotic syndrome.

E.2.2

Secondary objectives of the trial

To determine whether a six day course of oral prednisolone given at the time of URTI
i] reduces the overall rate of URTI-related relapse of nephrotic syndrome (expressed as relapses per year).
ii] reduces the overall rate of relapse of nephrotic syndrome (expressed as relapses per year).
iii] reduces the cumulative dose of prednisolone received over the 12 month study period.
iv] reduces the incidence and prevalence of adverse effects of prednisolone including behavioural abnormalities.
v] reduces the number of subjects undergoing escalation of background immunosuppressive therapy (e.g. addition of ciclosporin, tacrolimus, cyclophosphamide etc).
vi] increases the number of subjects undergoing reduction of background immunosuppressive therapy (e.g. cessation of ciclosporin or long term maintenance prednisolone therapy).
vii] is more cost effective than standard course therapy.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects aged over 1 year and less than 19 years will be eligible for inclusion if they have relapsing SSNS, defined as having experienced 2 or more relapses in the preceding 12 months. This will include the following groups:
• Subjects on no long-term immunosuppressive therapy;
• Subjects receiving long term maintenance prednisolone therapy at a dose of up to and including 15mg/m2 on alternate days. Note that this is the maximum dose at the time of recruitment – if children subsequently receive a higher dose e.g. after relapse, they can remain in the study;
• Subjects receiving long term maintenance prednisolone therapy at a dose of up to and including 15mg/m2 on alternate days in conjunction with other immunosuppressive therapies, including levamisole, ciclosporin, tacrolimus, MMF, mycophenolate sodium and azathioprine;
• Subjects receiving long-term immunosuppressive therapies, including levamisole, ciclosporin, tacrolimus, MMF, mycophenolate sodium and azathioprine without long term maintenance prednisolone therapy.
• Subjects who have previously received a course of oral or intravenous cyclophosphamide:
o Must have experienced two relapses in the 12 months prior to randomisation (in keeping with all other subjects)
o Must have experienced at least one of these relapses following completion of cyclophosphamide therapy
o Must be at least 3 months post completion of oral or intravenous cyclophosphamide therapy
• Subjects who have previously received a single dose or course of intravenous rituximab:
o Must have experienced two relapses in the 12 months prior to randomisation (in keeping with all other subjects)
o Must have experienced at least one of these relapses following completion of rituximab therapy
o Must be at least 3 months post completion of intravenous rituximab therapy
• Parents and (where age appropriate) subject understand the definition of URTI and the need to commence study drug once this definition has been met.
• Written informed consent obtained from the subject’s parents/guardians and written assent obtained from subject (where age appropriate). Subjects aged 16 years and above will provide their own written informed consent.

E.4

Principal exclusion criteria

• Subjects with steroid resistant nephrotic syndrome
• Subjects receiving, or within 3 months of completing a course of oral or intravenous cyclophosphamide
• Subjects receiving, or within 3 months of receiving a course of rituximab
• Subjects on daily prednisolone therapy at time of recruitment
• Subjects on a prednisolone dose of greater than 15mg/m2 on alternate days at time of recruitment
• Subjects with a documented history of significant non-adherence with medical therapy
• Subjects who will be transferred from paediatric to adult services during the 12 month study period.
• Subjects unable to take prednisolone tablets, even in crushed form.
• Known allergy to prednisolone

E.5 End points

E.5.1

Primary end point(s)

First URTI-related relapse of nephrotic syndrome during the 12 month follow-up period. Relapse is defined as Albustix positive proteinuria (+++ or greater) for 3 consecutive days or the presence of generalised oedema plus 3+ proteinuria. URTI-related relapse is defined as a relapse occurring within 14 days of the development of an URTI. First URTI-related relapse refers to the first URTI-related relapse which occurs within the 12 month study follow up period.

E.5.1.1

Timepoint(s) of evaluation of this end point

Patients will be follow-up at baseline, 3, 6, 9, and 12 months and details of any relapses that have occured will be documented at these time points.

E.5.2

Secondary end point(s)

i] Relapse rate (per year).
ii] Cumulative dose of prednisolone (mg/kg).
iii] Incidence of serious adverse events.
iv] Incidence of adverse events.
v] Incidence of behavioural change (as assessed by the Achenbach child behaviour checklist).
vi] Incidence of escalation of immunosuppressive therapy.
vii] Incidence of reduction of immunosuppressive therapy.
viii] Cost per relapse of proteinuria.
ix] Cost per QALY gained.

E.5.2.1

Timepoint(s) of evaluation of this end point

Patients will be follow-up at baseline, 3, 6, 9, and 12 months and details relating to any of the secondary end points be documented at these time points.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

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)

Yes

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

E.8.1.4

Double blind

Yes

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

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

113

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

6 months after LVLS to allow time for final data analysis and report writing.

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