Clinical Trials Register

Summary
EudraCT Number:	2011-003134-13
Sponsor's Protocol Code Number:	A551109
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2011-11-28
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

Netherlands - Competent Authority

A.2

EudraCT number

2011-003134-13

A.3

Full title of the trial

5-Aminolevulinic Acid PhotoDynamic Therapy for the treatment of premalignant disorders of the vulva.

5-Aminolevulinic acid fotodynamische therapie voor behandeling van premaligne aandoeningen van de vulva.

A.3.1

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

ALA-PDT for premalignant vulvar disorders.

ALA-PDT voor premaligne vulva aandoeningen.

A.3.2

Name or abbreviated title of the trial where available

ALA-PDT for premalignant vulvar disorders

ALA-PDT voor premaligne vulva aandoeningen

A.4.1

Sponsor's protocol code number

A551109

A.5.4

Other Identifiers

Name:

A551109

Number:

Unit TRC Dept. Urology Erasmus MC

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	Erasmus MC
B.1.3.4	Country	Netherlands
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	Erasmus MC
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Erasmus MC
B.5.2	Functional name of contact point	Dr. ir. L.J. Blok
B.5.3	Address:
B.5.3.1	Street Address	's-Gravendijkwal 230
B.5.3.2	Town/ city	Rotterdam
B.5.3.3	Post code	3015 CE
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+3110704 43 83n.a.
B.5.5	Fax number	n.a.n.a.n.a.n.a.
B.5.6	E-mail	l.blok@erasmusmc.nl

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	5-Aminolevulinic Acid
D.3.2	Product code	Not applicable
D.3.4	Pharmaceutical form	Gel
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	5-aminolevulinic acid hydrochloride
D.3.9.1	CAS number	5451-09-2
D.3.9.2	Current sponsor code	not applicable
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Aldara (Imiquimod)
D.2.1.1.2	Name of the Marketing Authorisation holder	Meda AB (Pipers väg 2A; 170 73 Solna; Sweden)
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Aldara 5% cream (Imiquimod)
D.3.4	Pharmaceutical form	Cream
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	IMIQUIMOD
D.3.9.1	CAS number	99011-02-6
D.3.9.2	Current sponsor code	not applicable
D.3.9.4	EV Substance Code	SUB12453MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
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.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
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	Dermovate cream 0,5 mg/g
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline BV (Huis ter Heideweg 62; 3705 LZ Zeist; The Netherlands)
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Dermovate
D.3.4	Pharmaceutical form	Cream
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	CLOBETASOL PROPIONATE
D.3.9.1	CAS number	25122-46-7
D.3.9.2	Current sponsor code	not applicable
D.3.9.4	EV Substance Code	SUB01346MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.05
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Premalignant vulvar disorders (usual type Vulvar Intraepithelial Neoplasia)

Premaligna vulvaire aandoeningen (usual type Vulvaire Intraepitheliale Neoplasie)

E.1.1.1

Medical condition in easily understood language

Premalignant vulvar disorders

Vulva aandoeningen die een voorstadium van vulvakanker zijn.

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	14.0
E.1.2	Level	PT
E.1.2	Classification code	10062135
E.1.2	Term	Vulval neoplasm
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 assess the efficacy of low dose rate light fractionated aminolevulinic acid-Photodynamic Therapy (ALA-PDT) for treatment of usual type Vulvar Intraepithelial Neoplasia (uVIN) and lichen sclerosus (LS).

Bepalen van de effectiviteit van lage dosering licht gefractioneerde Aminolevuline Zuur - Fotodynamische Therapie voor de behandeling van usual type Vulvaire Intraepitheliale Neoplasie (uVIN) en Lichen Sclerosus (LS).

E.2.2

Secondary objectives of the trial

To determine clearance of HPV after treatment of uVIN; to assess normalization immunocompetent cell counts and of expression of a number of markers (Ki67, p16, p53, mir-155) after treatment; to monitor pain during and after treatment; to monitor quality of life before and after treatment.

Bepalen van de klaring van HPV na behandeling van uVIN; bepalen van de normalisatie van immunocompetente cel aantallen en van de expressie van een aantal markers (Ki67, p16, p53, mir-155) na behandeling; monitoren van pijn tijdens en na de behandeling; monitoren van de kwaliteit van leven voor en na behandeling.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Histologically proven usual type VIN, without invasion or histologically proven LS.
- The patient is willing to use a medically acceptable method of contraception throughout the study.
- Age 18 and above.

- Histologisch bewezen uVIN, zonder invasie of histologisch bewezen.
- De patiënte is bereid een medisch acceptabele vorm van contraceptie te gebruiken fgedurende de studie.
- Leeftijd 18 jaar of ouder.

E.4

Principal exclusion criteria

- (Micro-)invasive carcinoma.
- Pregnancy and/or breastfeeding.
- Past history of vulvar cancer.
- Differentiated (non HPV-related) VIN.
- Other treatment of VIN, anogenital warts or LS within 1 month of start treatment.
- Hypersensitivity to any components of the cream formulations.
- History of psoriasis or other inflammatory dermatosis of the vulva.
- Insufficient understanding of the Dutch language.

- (Micro-)invasief carcinoom.
- Zwangerschap of borstvoeding.
- Vulvacarcinoom in de voorgeschiedenis.
- Gedifferentieerde (niet HPV-gerelateerde) VIN.
- Andere behandeling voor VIN, anogenitale wratten of LS binnen 1 maand van de start van de behandeling.
- Hypersensitiviteit voor een van de bestanddelen van de onderzoeksmedicatie.
- Psoriasis of andere inflammatoire dermatose van de vulva in de voorgeschiedenis.
- Onvoldoende kennis van de Nederlandse taal.

E.5 End points

E.5.1

Primary end point(s)

Clinical response to the treatment in VIN or LS lesions after the end of ALA-PDT treatment measured by 1) reduction in lesion size after the end of treatment as visualized with high resolution photographs, 2) histological regression of uVIN or LS to ‘normal’ vulvar tissue as visualized in H/E stained sections and 3) relieve of symptoms like itching and disorder-related pain.

Klinische respons van de VIN of LS laesies op de behandeling aan het einde van de ALA-PDT behandeling gemeten door 1) afgenomen laesiegrootte aan het eind evan de behandeling, gevisualiseerd d.m.v. hoge resolutie foto's, 2) histologische regressie van uVIN of LS tot ‘normaal’ vulvaweefsel gevisualiseerd m.b.v. H/E kleuring en 3) afname van symptomen zoals jeuk en ziekte-gerelateerde pijn.

E.5.1.1

Timepoint(s) of evaluation of this end point

Leeen s.v.p. invullen!

E.5.2

Secondary end point(s)

Normalization of immunocompetent cells numbers in the region of the disorder at 4 weeks after the end of treatment; clearance of HPV DNA in uVIN lesions at 4 weeks after treatment; normalization of expression levels of Ki67, p16 and p53 at 4 weeks after treatment; normalization of expression level of mir-155 at at 4 weeks after treatment; improvement of quality of life at 4 weeks after treatment; and assessment of treatment-induced pain.

Normalisatie van immunocompetente celaantallen in het gebied van de aandoening 4 weken na het eind van de behandeling; klaring van HPV DNA in uVIN laesies 4 weken na behandeling; normalisatie van expressie niveau van Ki67, p16 en p53 4 weken na behandeling; normalisatie van het expressie niveau van mir-155 4 weken na de behandeling; verbetering van de kwaliteit van leven 4 weken na de behandeling; bepaling van de behandelingsgerelateerde pijn.

E.5.2.1

Timepoint(s) of evaluation of this end point

4 weeks after treatment.

4 weken na de behandeling.

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

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

Quality of life, assessment of treatment induced pain

Kwaliteit van leven, beoordelen van pijn veroorzaakt door de behandeling

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

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)

Yes

E.8.2.2

Placebo

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

Last patient last visit.

Laatste patiënt, laatste visite.

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.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

180

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

If ALA-PDT is successfull patients who have not received this treatment will be offered treatment with ALA-PDT.

Als ALA-PDT succesvol blijkt te zijn, krijgen patiënten die deze behandeling niet hebben ontvangen de mogelijkheid alsnog met ALA-PDT te worden behandeld.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-11-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-02-13

P. End of Trial
P.	End of Trial Status	Ongoing

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