Clinical Trials Register

Summary
EudraCT Number:	2015-005820-24
Sponsor's Protocol Code Number:	IIS-PICATO1264
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-01
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2015-005820-24

A.3

Full title of the trial

A randomized study to evaluate the efficacy of ingenol mebutate on actinic keratoses and field cancerization compared to cryotherapy

Studio randomizzato per valutare l'efficacia di ingenolo mebutato rispetto alla crioterapia su cheratosi attiniche e campo di cancerizzazione

A.3.1

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

A study to evaluate the efficacy of ingenol mebutate on precancerosis and its contigous area compared to cryotherapy

studio per valutare l'efficacia di ingenolo rispetto alla terapia fisica crioterapia su precancerosi e aree contigua alla precancerosi

A.3.2

Name or abbreviated title of the trial where available

A study to evaluate the efficacy of ingenol mebutate on precancerosis and its contigous area compare

studio per valutare l'efficacia di ingenolo rispetto alla terapia fisica crioterapia su precancerosi

A.4.1

Sponsor's protocol code number

IIS-PICATO1264

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	A.O.U. Università degli Studi della Campania "Luigi Vanvitelli"
B.1.3.4	Country	Italy
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	LeoPharma
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	A.O.U. Seconda Università degli Studi di Napoli
B.5.2	Functional name of contact point	Clinica dermatologica
B.5.3	Address:
B.5.3.1	Street Address	Via Pansini,5
B.5.3.2	Town/ city	Napoli
B.5.3.3	Post code	80131
B.5.3.4	Country	Italy
B.5.4	Telephone number	0815666828
B.5.5	Fax number	0697625822
B.5.6	E-mail	g.argenziano@gmail.com

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	PICATO - 150 MICROGRAMMI/G-GEL-USO CUTANEO-TUBETTO (HDPE/ALU) 3 TUBETTI
D.2.1.1.2	Name of the Marketing Authorisation holder	LEO PHARMA A/S
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	picato
D.3.2	Product code	[042513010]
D.3.4	Pharmaceutical form	Gel
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Topical use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INGENOLO MEBUTATO
D.3.9.2	Current sponsor code	NA
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	142
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

actinic keratoses and field cancerization

Cheratosi attinica e campo di cancerizzazione

E.1.1.1

Medical condition in easily understood language

keratoses

Cheratosi

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10000614
E.1.2	Term	Actinic keratosis
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue 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

Evaluation of the clinical efficacy of ingenol mebutate gel versus cryosurgery in terms of number of AKs showing complete response and the effect of the two treatments on the cancerization field as measured using reflectance confocal microscopy

Lo studio si propone di valutare l'efficacia clinica di ingenolo mebutato gel rispetto alla crioterapia intesa come riduzione del numero di cheratosi attiniche (completa risoluzione) e come azione sul campo di cancerizzazione misurata attraverso microscopia confocale

E.2.2

Secondary objectives of the trial

Patient compliance;
Patient assessment of local tolerability and satisfaction to treatment;
Cosmetic outcome

Ulteriore obiettivo dello studio è quello di paragonare compliance, tollerabilità, livello di soddisfazione da parte del paziente e risultato cosmetico nei due trattamenti

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Current diagnosis of AK, with =2 lesions of grade I and/or II located in two different anatomical districts (within a contiguous 25 cm2 area on the face, scalp or forehead);
- Male = 18 years of age
- Female = 60 years of age ;
• Skin type I or II according to Fitzpatrick;
• Patient has confirmed his/her willingness to participate in this study after being informed of all aspects of the study that are relevant to his/her decision to participate, by signing and dating the approved informed consent form, according to ICH and local laws.
The 25 cm2 contiguous treatment areas could be of any shape, e.g. 5 cm x 5 cm, 2 cm x 12.5 cm, 3 cm x 8.3 cm.

- Pazienti con diagnosi di cheratosi attiniche con 2 o più lesioni di grado I e/o II localizzate in due differenti aree anatomiche (all'intero di un area contigua di 25 cm2 di volto, cuoio capelluto o fronte)
- Uomini con età = 18 anni
- Donne con età > 60 anni
- Fototipo I o II secondo Fitzpatrick
- Pazienti che hanno confermato la loro volontà di partecipare allo studio dopo essere stati informati di tutti cli aspetti dello studio stesso ed aver firmato il consenso informato.
NB L'area contigua di 25cm2 può essere di qualsiasi forma ( 5 cm x 5 cm, 2 cm x 12.5 cm, 3 cm x 8.3 cm)

E.4

Principal exclusion criteria

• Has received any therapy for AK within the past 3 months
• Has AK of grade III
• Has currently a skin cancer or shows an early stage of skin cancer;
• Has another skin disease that requires treatment with other medications in the AK area or in distance of 3 cm;
• Use of cosmetic or therapeutic products and procedures which could interfere with assessments of the treatment area;
• Immunosuppressive therapies or current treatment for cancer;
• Clinically unstable medical condition;
• High risk group for HIV infection or presentation of other infectious diseases (HAV, HBV, HCV, TBC, etc);
• Allergies to the tested gel (ingenol mebutate and eccipients);
• Pregnancy and breastfeeding;
• Psychiatric disease that may interfere with follow-up of study procedures;
• Participation in other clinical trials up to 30 days prior to day 1 of the study;
• Patient is, for any reason, considered by the investigator to be an unsuitable candidate for the study

Panzienti che:
-si sono sottoposti a qualsiasi altro trattamento nei precedeni 3 mesi
- presentano cheratosi attiniche di grado III
- sono affetti contemporaneamente da un tumore cutaneo o una fase precoce di tumore cutaneo
- sono affetti da un'altra patologia cutanea che richiede applicazione di altri farmaci all'interno dell'area delle cheratosi attiniche o ad una distanza minore di 3 cm
- uso di terapie o cosmetici nell'area del trattameno che possono interferire con la valutazione dell'efficacia
- contemporanee terapie immunosoppressive o chemioterapie
- condizione clinica instabile
- appartenenza a gruppo ad alto rischio per HIV o manifestazioni di altra patologia infettiva HAV, HBV, HCV, TBC, etc)
- allergia al farmaco in uso (ingenolo mebutato)
- gravidanza e allatamento
- qualsiasi patologia psichiatrica che possa interferire con il follow-up
- partecipazione ad un altro studio clinico nel mese precedente all'arruolamento nello studio
- pazienti che per qualsiasi motivo sono considerati non candidabili allo studio a giudizio dell'investigatore

E.5 End points

E.5.1

Primary end point(s)

At least 75% reduction in the total AK count relative to baseline
Reduction of subclinical AK lesions according to a RCM score

Riduzione del 75% del numero totale di cheratosi attiniche rispetto al tempo 0, riduzione del numero di cheratosi attiniche subcliniche secondo lo score con microscopia confocale

E.5.1.1

Timepoint(s) of evaluation of this end point

At month 1 and month 6

Dopo un mese dal trattamento e con un follow-up a sei mesi dal trattamento

E.5.2

Secondary end point(s)

Absence of new lesions after a follow-up period of 6 months
Cosmetic outcome.

Assenza di nuove lesioni dopo un periodo di follow-up di 6 mesi
Risultato cosmetico

E.5.2.1

Timepoint(s) of evaluation of this end point

At month 6

A 6 mesi dal trattamento

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

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

• Patient compliance;
• Patient assessment of local tolerability and satisfaction to treatment;
• Cosmetic outcome

Compliance, tollerabilità e risultato estetico

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

Terapia fisica ossia crioterapia (applicata con un tempo di congelamento di 5 secondi su ogni lesion

cryosurgery (applied for a freeze time of 5 seconds, on each lesion included in an area of 25 cm2).

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

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

Information not present in EudraCT

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

LVLS

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:

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

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

follow up visits

Controlli ambulatoriali

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

2016-09-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-03-03

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

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