Clinical Trials Register

Summary
EudraCT Number:	2013-003107-19
Sponsor's Protocol Code Number:	13-0288
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-04-11
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

2013-003107-19

A.3

Full title of the trial

Phase II clinical trial investigating the use of epigallocatechin-3-gallate (Veregen) in the treatment of vulval intraepithelial neoplasia

A.3.1

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

A trial to investigate the use of Veregen ointment in the treatment of vulval intraepithelial neoplasia, a severe skin disorder that may lead to vulval cancer.

A.3.2

Name or abbreviated title of the trial where available

EPIVIN trial (v 1.0)

A.4.1

Sponsor's protocol code number

13-0288

A.5.4

Other Identifiers

Name:

CRCTU CAS number

Number:

VU2001

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 Birmingham
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	Medigene
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	NIHR RfPB
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	Cancer Research UK Clinical Trials Unit
B.5.2	Functional name of contact point	Clive Stubbs
B.5.3	Address:
B.5.3.1	Street Address	School of Cancer Sciences, University of Birmingham
B.5.3.2	Town/ city	Birmingham
B.5.3.3	Post code	B15 2TT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01214147671
B.5.5	Fax number	01214142230
B.5.6	E-mail	c.stubbs@bham.ac.uk
B.Sponsor: 2
B.1.1	Name of Sponsor	Sandwell and West Birmingham Hospitals NHS 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 RfPB
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	Medigene
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sandwell and West Birmingham Hospitals NHS Trust
B.5.2	Functional name of contact point	Jocelyn Bell
B.5.3	Address:
B.5.3.1	Street Address	R&D Governance, City Hospital, Dudley Road,
B.5.3.2	Town/ city	Birmingham
B.5.3.3	Post code	B18 7QH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01215074811
B.5.5	Fax number	01215074945
B.5.6	E-mail	jocelyn.bell@nhs.net

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	Veregen
D.2.1.1.2	Name of the Marketing Authorisation holder	Medigene
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Veregen 10% ointment
D.3.4	Pharmaceutical form	Ointment
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Epigallocatechin gallate (EGCG)
D.3.9.1	CAS number	188265-33-0
D.3.9.3	Other descriptive name	Camellia sinensis (green leaf)
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10%
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	Yes
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	Ointment
D.8.4	Route of administration of the placebo	Cutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Vulval intraepithelial neoplasia (VIN)

E.1.1.1

Medical condition in easily understood language

Changes that occur in the skin cells of the vulva that cause symptoms, associated with a viral infection by HPV, that may develop into vulval cancer if untreated.

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	LLT
E.1.2	Classification code	10057313
E.1.2	Term	Vulval intraepithelial neoplasia grade III
E.1.2	System Organ Class	100000004864

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 of this clinical trial is to determine whether topical application of EGCG (Veregen) can lead to histological resolution of VIN. This is done by comparing tissue biopsies taken before and after Veregen treatment.

E.2.2

Secondary objectives of the trial

The secondary objectives are to evaluate in women undergoing treatment with Veregen
1. clinical responses using the RECIST criteria v1.1
2. the number of treatment withdrawals/dose reductions
3. toxicity according to NCI CTCAE v4.0
4. relief of clinical symptoms and improvement in quality of life using a validated quality of life questionnaires (DLQI) developed by the Department of Dermatology and Wound Healing, University of Cardiff.
5. the number of women requiring further treatment within 12 months of study entry

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

≥ 18 years of age, histological confirmation of "usual"-type vulval intraepithelial neoplasia (VIN3)*, at least one lesion that can be accurately measured (using the RECIST 1.1 criteria) in at least one dimension with longest diameter ≥ 20 mm, using a reliable method of contraception (excluding condoms), written informed consent to participate in the trial.
*All histological material generated by this study will be assessed by Specialist Consultant in Gynaecological Pathology; 10% of biopsies will be independently reviewed by a second pathologist

E.4

Principal exclusion criteria

Suspected anogenital carcinoma or those considered by the attending clinician to be at high risk of developing invasive disease; pregnant, breast feeding or trying to conceive; treated for VIN within the previous four weeks; known allergy to Veregen or any of its components; patients suffering from immunosuppressive disorder or taking immunosuppressives; unable to comply with the protocol.

E.5 End points

E.5.1

Primary end point(s)

Proportion of women with histological resolution of VIN as established by blinded pathology review.

E.5.1.1

Timepoint(s) of evaluation of this end point

At Week 32 after entering the study. Treatment with active ointment or placebo will have ceased at Week 16.

E.5.2

Secondary end point(s)

Histological resolution at 16 weeks*;
Clinical resolution (RECIST 1.1);
Time to clinical resolution;
Toxicity (CTC AE v4.0);
Drug compliance (including ineligibility and withdrawal);
Need for further treatment and time to further treatment;
Patient acceptability using:(1) Pain/pruritus assessment with McGill’s questionnaires and assessment of cumulative treatment (The number of treatment withdrawals/dose reductions), and (2) Dermatology Quality of life questionnaire (DLQI).

*To supplement the primary outcome the number (%) of patients with histological resolution at 32 weeks shall be contrasted against the 16 week histology results.

E.5.2.1

Timepoint(s) of evaluation of this end point

Histological resolution at 16 weeks; the rest of the secondary endpoints will be assessed at the 32-week point.

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

Yes

E.6.13.1

Other scope of the trial description

Compliance

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

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

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

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 the trial will be 3 months after the last visit of the last subject, ie, the last data capture.This will allow sufficient time for the completion of protocol procedures, data collection and data input. The Trials Office will notify the MHRA and main REC that the trial has ended and will provide them with a summary of the clinical trial report within 12 months of the end of trial.

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