Clinical Trials Register

Summary
EudraCT Number:	2016-002088-33
Sponsor's Protocol Code Number:	PER-DIC-16-001
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-11-04
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

2016-002088-33

A.3

Full title of the trial

Impact and Costs of Health Care Education, Phone Reminders and enhanced follow-up intervention on Prescription adherence, Treatment Satisfaction and Effectiveness in patients with Multiple Actinic Keratosis treated with diclofenac in hyaluronic acid gel 3% (Solaraze 3%). No-profit study.

Impatto e costi di un intervento integrato basato su educazione sanitaria, promemoria telefonici, e follow-up intensificati sull’aderenza, soddisfazione ed efficacia terapeutica in pazienti con cheratosi attinica (AK) in terapia con diclofenac 3% gel in acido ialuronico (Solaraze 3%)

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

PER-DIC-16-001

A.4.1

Sponsor's protocol code number

PER-DIC-16-001

A.5.4

Other Identifiers

Name:

PER-DIC-16-001

Number:

PER-DIC-16-001

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	FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS UNIVERSITA' CATTOLICA DEL SACRO CUORE
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	Almirall spa
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	Clinical Trial Center SPA
B.5.2	Functional name of contact point	Unità CRO
B.5.3	Address:
B.5.3.1	Street Address	L.GO GEMELLI 8
B.5.3.2	Town/ city	ROMA
B.5.3.3	Post code	00168
B.5.3.4	Country	Italy
B.5.4	Telephone number	0630157321
B.5.6	E-mail	elena.carafelli@clinicaltrialcenter.it

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	SOLARAZE - "3% GEL" 1 TUBO DA 60 G GEL
D.2.1.1.2	Name of the Marketing Authorisation holder	ALMIRALL S.A.
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	SOLARAZE
D.3.2	Product code	[ND]
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	DICLOFENAC SODICO
D.3.9.2	Current sponsor code	ND
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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.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	SOLARAZE - "3% GEL" 1 TUBO DA 60 G GEL
D.2.1.1.2	Name of the Marketing Authorisation holder	ALMIRALL S.A.
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	SOLARAZE
D.3.2	Product code	[ND]
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	DICLOFENAC SODICO
D.3.9.2	Current sponsor code	ND
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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

Multiple Actinic Keratosis

CHERATOSI ATTINICA

E.1.1.1

Medical condition in easily understood language

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

to evaluate the efficacy of an integrated low-intensity intervention program against standard-of-care on treatment adherence among patients with multiple AK receiving diclofenac in hyaluronic acid gel 3% (Solaraze 3%).

Valutare l’efficacia di un intervento integrato a bassa intensità, rispetto all’intervento standard, sull’aderenza alla terapia in pazienti affetti da cheratosi attiniche multiple in terapia con diclofenac 3% gel in acido ialuronico (Solaraze 3%).

E.2.2

Secondary objectives of the trial

to evaluate the efficacy of an integrated low-intensity intervention program against standard-of-care on:
- Patient’s complete and partial Lesion Clearance Rate at the end of treatment (3-months);
- Patient’s complete and partial Sustained Lesion Clearance Rate (at 6- and 12- month);
- Patient’s Complete Lesion Clearance Rate (at 3-, 6- and 12-month).
- Treatment Satisfaction at the end of treatment (at 3-month);
- Impact of AK on Quality of Life (at 3-month);
- Local Skin Reaction (LSR) score (3-month);
- Direct Cost of Intervention (at 3-month);
- To create the content and editing of the educational material and the phone reminder (before RCT starts)

valutare l’efficacia di un programma di intervento integrato a bassa intensità rispetto alla terapia standard, circa:
- Il tasso di guarigione completa e parziale della lesione alla fine del trattamento (3 mesi).
- Il tasso di guarigione completa e parziale della lesione persistente (a 6 e a 12 mesi).
- Il tasso di guarigione completa della lesione (a 3. 6 e 12 mesi).
- La soddisfazione dei pazienti per la terapia alla fine del trattamento (a 3 mesi).
- L’impatto di AK sulla qualità di vita (a 3 mesi).
- Il punteggio relativo alla valutazione della Reazione Dermica Locale (Local Skin Reaction-LSR) ( a 3 mesi).
- Il costo diretto dell’intervento (a 3 mesi).
- Realizzare il contenuto e l’editoria del materiale educativo e del promemoria telefonico (SMS) (prima dell’avvio dello studio clinico).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients with clinically typical, visible and discrete multiple AK, grade I/II according to Olsen’s classification, in a skin area of 50 cm2, for whom the treating dermatologist has prescribed diclofenac in hyaluronic acid gel 3% (Solaraze 3%). Those patients should have not started the treatment before the inclusion in the present study .
2. Willing to participate in the study and able to provide informed consent.
3. Age = 18 years
4. Able to read and write in Italian Language
5. Women with childbearing potential willing not to start a pregnancy during the course f the study and for 1 month after the conclusion of the treatment
6. Men having relationships with women with childbearing potential willing not to procure a pregnancy during the course of the study and for 1 month after the conclusion of the treatment.

1. Pazienti adulti affetti da AK clinicamente tipica, visibile, discreta e multipla di grado I/II secondo la classificazione di Olsen, in un’area dermica di 50 cm2, per la quale il dermatologo abbia prescritto una terapia topica con diclofenac 3% gel in acido ialuronico (Solaraze 3%). Quei pazienti non dovrebbero aver iniziato il trattamento prima dell’inclusione nello studio.
2. Intenzione a partecipare allo studio ed a fornire il consenso informato.
3. Età = 18 anni
4. In grado di leggere e scrivere in italiano.
5. Donne in età fertile che non abbiano intenzione di iniziare una gravidanza durante lo studio e per il mese successivo la conclusione del trattamento.
6. Uomini che non abbiano intenzione di procurare una gravidanza a donne in età fertile durante lo studio e per il mese successivo la conclusione del trattamento

E.4

Principal exclusion criteria

1. Unable to understand and execute simple instructions or patients in need of assistance from a caregiver (professional or non-professional) for the application of topical medication.
2. Patients immunocompromised as per medical history (i.e. iatrogenic immunosuppression, HIV / AIDS)
3. Any major surgery or major clinical events (i.e. ictus cerebri, myocardial infarction, etc) in the month prior to screening (may affect Patient-Reported Outcomes)
4. Previous treatments with field-directed therapy in the past 3 months before the screening.
5. Aspirin-sensitive patients, due to possible cross-reactivity with diclofenac in hyaluronic acid gel 3% (Solaraze %).
6. Pregnant and breast-feeding women
7. Forecast of moving to another region within the next 12 months following the potential inclusion in the study.

1. Incapacità di comprendere ed eseguire semplici istruzioni o pazienti che necessitino di assistenza da parte di un badante (professionale o non-professionale) per l’applicazione del farmaco topico.
2. Pazienti immunocompromessi come da storia medica (es. immunodepressione iatrogenica, HIV/AIDS, etc).
3. Qualsiasi intervento di chirurgia importanti o eventi clinici maggiori (es. ictus cerebrale, infarto miocardico, ecc.) nel mese precedente allo screening (può influenzare i relativi Patient Reported Outcomes, ovvero i dati riferiti dl paziente ).
4. Precedenti trattamenti con terapie dirette al campo di cancerizzazione negli ultimi 3 mesi prima dello screening.
5. Pazienti intolleranti all’aspirina a causa di possibile cross-reattività con diclofenac 3% gel in acido Ialuronico (Solaraze 3%).
6. Donne in gravidanza o allattamento.
7. Previsione di trasferirsi in un’altra regione entro i successivi 12 mesi dalla potenziale inclusione nello studio.

E.5 End points

E.5.1

Primary end point(s)

To define the Adherence to the treatment regimen as product use greater than 80% of prescribed dose, and will be calculated according to the Formula: A= [(Wb-We)/Wnb] x 100, where Wb is the gross weight at baseline, We is the gross weight at the end of self-administration, Wnb is the product net nominal weight at baseline.

l’ aderenza al regime di trattamento sarà definita da un consumo di prodotto maggiore dell’80% rispetto alla dose prescritta secondo A=[(Wb- We)/Wnb] x 100, dove A è la percentuale del peso netto del prodotto usato, Wb è il peso lordo del prodotto al basale e We è il peso lordo del prodotto alla fine del trattamento e Wnb è il peso netto nominale del prodotto consegnato al paziente .

E.5.1.1

Timepoint(s) of evaluation of this end point

12 Months

12 mesi

E.5.2

Secondary end point(s)

1. 3-months Lesion Clearance Rate: the rate of lesion clearance will be defined as the ratio between the number of residual AK lesion count and baseline AK count in the treated area
2. 6-months and 12-months Sustained Lesion Clearance Rate: the rate of sustained lesion clearance will be defined as the ratio between the number of residual AK lesion count at each time point and baseline AK count in the treated area.
3. Patient’s Complete Clearance Rate at 3, 6 and 12 months: patient’s complete clearance is defined as clearance of all AK lesions identified at baseline.
4. Patient’s Partial Clearance Rate at 3, 6 and 12 months: patient’s partial clearance is defined as clearance of 75% of AK lesions identified at baseline.
5. Treatment Satisfaction on Medication (3 items) (included in the AK QoL)
6. Quality of Life: AK-QOL questionnaire;
7. Local Skin Reaction; LSR score will be evaluated with a 6 items scale (Lebowhol et al., 2012).
8. Intervention Costs per patient. Direct cost will be considered the cost of all medical encounters including extra-visits and phone consultations, health education brochure, sms reminders, product wastage (weight of unused product). The cost incurred for study outcome evaluation (i.e. evaluation of LSR, tube weighting, assessment of lesion clearance) will not be included. Medical encounters will be defined as very short (t<5’), short (5’<t<10’), normal (10’<t<15’), long (15’<t<20’) or very long (t>20’). At the end of each interaction, the attending physicians will record the approximate duration of each visit at first in the ad hoc form and then in the eCRF.
9. The content and editing of the educational material used for the RCT.

1. Il tasso di guarigione della lesione a 3 mesi: il tasso di guarigione della lesione sarà definito dal rapporto tra il numero di lesioni attiniche residue e quelle osservate al basale nell’area trattata.
2. Il tasso di guarigione delle lesioni persistenti a 6 e 12 mesi: il tasso di guarigione delle lesioni persistenti sarà definito dal rapporto tra il numero di lesioni attiniche residue ad ogni visita e quelle osservate al basale nell’area trattata.
3. Il tasso di completa guarigione a 3, 6 e 12 mesi: la completa guarigione del paziente è definita come la guarigione di tutte le lesioni di AK identificate al basale .
4. Il tasso di parziale guarigione a 3, 6, e 12 mesi: la parziale guarigione del paziente è definita dalla guarigione del 75% delle lesioni di AK identificate al basale .
5. La soddisfazione al trattamento medico (3 voci)(inclusi nel questionario AKQOL).
6. Qualità di Vita: questionario AK-QOL.
7. Reazione Dermica Locale (LSR): il punteggio LSR sarà valutato con una scala di 6 voci (Lebowhol et al., 2012).
8. Costi dell’ intervento per paziente: il costo diretto sarà valutato dall’ insieme dei costi relativi ai singoli interventi medici, incluse le visite extra ed i contatti telefonici, la brochure educativa, i promemoria fatti tramite SMS , il prodotto sprecato (peso di prodotto inutilizzato). I costi inerenti la valutazione dei risultati dello studio (es. La valutazione di LSR, la pesatura del prodotto, la valutazione di guarigione della lesione) non saranno inclusi. Gli incontri con il medico saranno definiti come: molto corti (t<5’), corti (5’<t<10’), normali (10’<t<15’), lunghi (15’<t<20’) o molto lunghi (t>20’). Il medico che effettuerà la visita, ne riporterà la durata approssimativa nell’apposito documento fonte e poi nella eCRF ,alla fine di ognuna di queste.
9. il contenuto e l’editoria del materiale educativo usato per lo studio clinico (RCT).

E.5.2.1

Timepoint(s) of evaluation of this end point

12 MONTHS

12 MESI

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

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)

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

STESSO FARMACO STESSO DOSAGGIO MA CON DIVERSO MONITORAGGIO CLINICO

SAME DRUG WITH SAME DOSAGE BUT WITH DIFFERENT MEDICAL MONITORING

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

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2020-11-04.

Yes

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

182

F.4.2

For a multinational trial

F.4.2.1

In the EEA

182

F.4.2.2

In the whole clinical trial

182

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)

STANDARD OF CARE

NORMALE PRATICA CLINICA

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

2016-09-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-07-13

P. End of Trial
P.	End of Trial Status	Completed

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