Clinical Trials Register

Summary
EudraCT Number:	2016-000467-16
Sponsor's Protocol Code Number:	SP14019-18
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-03-18
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

Spain - AEMPS

A.2

EudraCT number

2016-000467-16

A.3

Full title of the trial

EVALUATION OF SP14019-F-01 TOPICAL SOLUTION FOR THE TREATMENT OF ATOPIC DERMATITIS. PILOT STUDY (CYCLATOP STUDY)

EVALUACIÓN DE LA SOLUCIÓN DE USO CUTÁNEO SP14019-F-01 PARA EL TRATAMIENTO DE LA DERMATITIS ATÓPICA. ESTUDIO PILOTO (ESTUDIO CYCLATOP)

A.3.1

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

EVALUATION OF SP14019-F-01 TOPICAL SOLUTION FOR THE TREATMENT OF ATOPIC DERMATITIS. PILOT STUDY (CYCLATOP STUDY)

EVALUACIÓN DE LA SOLUCIÓN DE USO CUTÁNEO SP14019-F-01 PARA EL TRATAMIENTO DE LA DERMATITIS ATÓPICA. ESTUDIO PILOTO (ESTUDIO CYCLATOP)

A.3.2

Name or abbreviated title of the trial where available

CYCLATOP STUDY

A.4.1

Sponsor's protocol code number

SP14019-18

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	Spherium Biomed
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Spherium Biomed
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Spherium Biomed
B.5.2	Functional name of contact point	Project Manager
B.5.3	Address:
B.5.3.1	Street Address	C/ Joan XXIII, 10
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08950
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34935093230
B.5.6	E-mail	bsantos@spheriumbiomed.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	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	Cyclosporine A
D.3.2	Product code	SP14019-F-01
D.3.4	Pharmaceutical form	Cutaneous spray, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Topical use (Noncurrent) Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CICLOSPORIN
D.3.9.1	CAS number	59865-13-3
D.3.9.2	Current sponsor code	SP14019-F-01
D.3.9.3	Other descriptive name	ciclosporin A
D.3.9.4	EV Substance Code	SUB06250MIG
D.3.10	Strength
D.3.10.1	Concentration unit	ml/cm2 millilitre(s)/square cm
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.002
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	Cutaneous solution
D.8.4	Route of administration of the placebo	Topical use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Atopic dermatitis

Dermatitis atopica

E.1.1.1

Medical condition in easily understood language

Atopic dermatitis

Dermatitis atopica

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	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10003639
E.1.2	Term	Atopic dermatitis
E.1.2	System Organ Class	100000004858

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 SP14019-F-01 topical solution (5% cyclosporine A [CsA]) compared to placebo topical solution for the treatment of patients with mild to moderate atopic dermatitis (AD).

Evaluar la eficacia de la solución tópica SP14019-F-01 (ciclosporina A [CsA] al 5 %) en comparación con la solución tópica placebo para el tratamiento de pacientes con dermatitis atópica (DA) leve a moderada.

E.2.2

Secondary objectives of the trial

To evaluate the safety and tolerability of SP14019-F-01 (5% CsA) topical solution in patients with mild to moderate AD.

Evaluar la seguridad y tolerabilidad de la solución tópica SP14019-F-01 (CsA al 5 %) en pacientes con DA leve a moderada.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female aged between 2 and 75 years, inclusive, at the screening visit.
2. AD diagnosis according to the Hanifin/Rajka criteria with one eczema outbreak at the screening and baseline.
3. Presence of at least two lesional areas. These areas should be at the left and right side of the body and occupying a body surface area (BSA) in each side between 0.1% and 10% of the BSA. IGA score of the two sites not differ by more than 1 point.
4. Mild to moderate disease severity of AD defined by an IGA score of 2 or 3 at baseline (IGA scale from 0 to 4).
5. Total BSA of AD involvement ? 10% in each side of the body (? 20% maximum).
6. Normal weight as defined by a Quetelet Index (Body Mass Index [BMI]: weight in kg divided by the square of height in meters) of 18.0 to 30.0 kg/m2 (both included).
7. General medical condition, in the investigator's opinion, does not interfere with the assessments and the completion of the trial.
8. Parent?s or legal guardian?s written informed consent and child assent, if appropriate or patient?s inform consent for patients ? 18 years of age before any assessment is performed.
9. Able to communicate with the investigator and comply with the requirements of the study (for children the parent can assist when necessary).

1. Pacientes con edades comprendidas entre 2 y 75 años, inclusive, en la visita de selección.
2. Diagnóstico de DA de acuerdo con los criterios de Hanifin-Rajka con un brote de eccema en la fase de selección y en la visita basal (visita 0).
3. Presencia de al menos dos zonas con lesión. Estas zonas deben estar en el lado izquierdo y derecho del cuerpo y deben ocupar una superficie corporal (SC) en cada lado de entre el 0,1 % y el 10 %. La puntuación IGA de las dos zonas no puede variar en más de 1 punto.
4. Gravedad de la DA leve a moderada definida por una puntuación IGA de 2 o 3 en la visita basal (escala IGA de 0 a 4).
5. SC total afectada ? 10 % en cada lado del cuerpo (? 20 % máximo).
6. Peso normal definido por un índice de Quetelet (índice de masa corporal [IMC]: peso en kg dividido por el cuadrado de la estatura en metros) de 18,0 a 30,0 kg/m2 (ambos incluidos).
7. Que el estado de salud general, según la opinión del investigador, no interfiera con las evaluaciones y la realización completa del estudio.
8. Consentimiento informado por escrito de los padres o del representante legal y conformidad del niño, si es necesario, o consentimiento informado del paciente cuando este tenga ? 18 años de edad antes de proceder a cualquier evaluación.
9. Capacidad de comunicarse con el investigador y de cumplir todas las obligaciones del estudio (cuando se trate de niños, los padres podrán ayudar cuando sea necesario).

E.4

Principal exclusion criteria

1. Female subject of childbearing potential without use of effective birth control methods, or not willing to continue practicing these birth control methods for at least 30 days after the end of the treatment period;
Note: Estrogen based hormonal contraception may not be reliable when SP14019-F-01 topical solution is applied, therefore to be eligible for this trial, women of childbearing potential should either:
a. use a double barrier method to prevent pregnancy (i.e., using a condom with either diaphragm or cervical cap);
b. use hormonal based contraceptives in combination with a barrier contraceptive (i.e., male condom, diaphragm or cervical cap, or female condom);
c. use an intrauterine device in combination with a barrier contraceptive (i.e., male condom, diaphragm or cervical cap, or female condom);
d. be only non-heterosexually active, practice heterosexual abstinence, or have a vasectomized partner (confirmed sterile).
Women with tubal ligation are required to use 1 non-hormonal contraceptive method.
Women who are postmenopausal for at least 2 years, and women with total hysterectomy are considered of non-childbearing potential.
Males with partners of childbearing potential should inform them of their participation in this clinical study and use a highly effective method of birth control during the study.
2. A positive pregnancy test or breast feeding at screening or at baseline.
3. Any condition in the lesions that in the opinion of the investigator could interfere with clinical assessments, e.g. acne, infection, rash other than AD, sunburn, scars, hairy or tattooed area.
4. Patients receiving phototherapy or systemic therapy for AD within 4 weeks before the first application of trial medication.
5. Patients receiving antibiotics, topical therapy for AD within 2 weeks before the first application of trial medication.
6. Patients taking antihistamines within 1 week before the first application of trial medication.
7. Patients receiving radiation therapy, systemic therapy with cytostatics or immunosuppressive drugs within 24 weeks before the first application of trial medication, or with previous history of malignancy (excluding basal cell carcinoma).
8. Patients with any acute skin infection (superinfection or secondary impetiginisation).
9. Patients with confirmed hypertension, renal disease or serious infections at screening.
10. Any currently active allergy such as but not limited to drug allergy, food allergy or hay fever.
11. Previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the trial medication administered in this trial (Gantrez ES-425 [Poly(methyl vinyl ether/maleic anhydride], ethanol, Propylene glycol, Transcutol (Diethylene Glycol Monoethyl Ether), Tween 80, MCT, Triacetin).
12. Participation in an investigational drug trial within 30 days prior to the first application of trial medication.
13. Any condition (including but not limited to alcohol and drug use), which in the opinion of the investigator could compromise the patient safety or compliance with trial procedures.

1. Mujer en edad fértil que no use métodos anticonceptivos eficaces o no esté dispuesta a seguir utilizando estos métodos anticonceptivos durante al menos 30 días después de finalizar el periodo de tratamiento.
Nota: un método anticonceptivo hormonal estrogénico puede no ser fiable cuando se aplica la solución tópica SP14019-F-01, por tanto, para poder participar en este estudio, las mujeres en edad fértil deben:
a. Usar un método de doble barrera para evitar un embarazo (es decir, usar un preservativo con diafragma o capuchón cervical).
b. Usar anticonceptivos hormonales en combinación con un anticonceptivo de barrera (es decir, preservativo, diafragma, capuchón cervical o condón femenino).
c. Usar un dispositivo intrauterino (DIU) en combinación con un anticonceptivo de barrera (es decir, preservativo, diafragma o capuchón cervical o condón femenino).
d. No ser solo heterosexualmente activo, practicar la abstinencia heterosexual o tener una pareja sometida a vasectomía (confirmada estéril).
Las mujeres con ligadura de trompas deben utilizar 1 método anticonceptivo no hormonal.
A las mujeres posmenopáusicas desde hace un mínimo de 2 años y a las mujeres que se han sometido a una histerectomía total no se las considera en edad fértil.
Los varones con pareja en edad fértil deben informar a su pareja sobre su participación en este estudio clínico y utilizar un método anticonceptivo altamente eficaz durante el estudio.
2. Prueba de embarazo positiva o lactancia en la fase de selección o en la visita basal.
3. Cualquier afección en las lesiones que, en opinión del investigador, pudiera interferir con las evaluaciones clínicas, p. ej., acné, infección, erupción aparte de DA, quemaduras solares, cicatrices, zonas con vello o tatuajes.
4. Pacientes que hayan recibido fototerapia o tratamiento sistémico para la DA en las 4 semanas anteriores a la primera aplicación de la medicación del estudio.
5. Pacientes que hayan recibido antibióticos o tratamiento tópico para la DA en las 2 semanas anteriores a la primera aplicación de la medicación del estudio.
6. Pacientes que hayan tomado antihistamínicos en la semana anterior a la primera aplicación de la medicación del estudio.
7. Pacientes que hayan recibido radioterapia, tratamiento sistémico con fármacos citostáticos o inmunosupresores en las 24 semanas anteriores a la primera aplicación de la medicación del estudio, o con antecedentes previos de neoplasia maligna (excluyendo el carcinoma basocelular).
8. Pacientes con una infección cutánea aguda (superinfección o impetiginización secundaria).
9. Pacientes con hipertensión, nefropatía o infecciones graves diagnosticadas en la fase de selección.
10. Cualquier alergia activa actualmente, como alergia a medicamentos, alergia a alimentos o rinitis alérgica, entre otras.
11. Alergia o hipersensibilidad clínicamente significativas diagnosticadas con anterioridad a cualquiera de los excipientes de la medicación administrada en este estudio (Gantrez ES-425 [Poli(metil vinil éter/anhídrido maleico], etanol, propilenglicol, transcutol (éter monoetílico de dietilenglicol), Tween 80, TCM, triacetina).
12. Participación en un estudio con un fármaco en investigación en los 30 días anteriores a la primera aplicación de la medicación del estudio.
13. Cualquier enfermedad (incluido, entre otros, el uso de alcohol y drogas), que, en opinión del investigador, pueda afectar a la seguridad del paciente o al cumplimiento con los procedimientos del estudio.

E.5 End points

E.5.1

Primary end point(s)

Efficacy endpoints:
- Absolute change from baseline (Visit 0) of Eczema Area and Severity Index (EASI) score of the treated body area (CsA vs Vehicle control placebo) from Visit 0 to Visit 1, Visit 2, Visit 3 and Visit 4.
- Absolute change from baseline (Visit 0) of Investigator?s Global Assessment (IGA) score (on a 0 to 4-point scale; CsA vs Vehicle control placebo) from Visit 0 to Visit 1, Visit 2, Visit 3 and Visit 4.
- Absolute change from baseline (Visit 0) of Atopic Dermatitis severity index (ADSI) score (Cs vs Vehicle control placebo) from Visit 0 to Visit 1, Visit 2, Visit 3 and Visit 4.

Safety endpoints:
- Frequency and severity of treatment-emergent adverse events (TEAEs).
- Frequency and severity of TEAEs leading to study drug discontinuation from Visit 0 through Visit 4.
- CsA plasma concentrations

Eficacia:
? Cambio absoluto en la puntuación EASI de la zona del cuerpo tratada (CsA vs. placebo) desde la visita basal (visita 0) hasta las visitas 1, 2, 3 y 4.
? Cambio en la puntuación IGA (en una escala de 0 a 4 puntos; CsA vs. placebo) desde la visita basal (visita 0) hasta las visitas 1, 2, 3 y 4.
? Cambio absoluto en la puntuación ADSI (CsA vs. placebo) desde la visita basal (visita 0) hasta las visitas 1, 2, 3 y 4.

Seguridad:
? Frecuencia y gravedad de los acontecimientos adversos (AA) aparecidos durante el tratamiento.
? Frecuencia y gravedad de los AAs que causan la suspensión de la medicación del estudio desde la visita 0 hasta la visita 4.
? Concentraciones plasmáticas de CsA.

E.5.1.1

Timepoint(s) of evaluation of this end point

Timepoints are detailed in section E.5.1.

Detallados en la seccion E.5.1.

E.5.2

Secondary end point(s)

As the study is exploratory, it is not necessary to classify endpoints as primary or secondary. All endpoints and timepoints have been detailed in section E.5.1.

Dado que se trata de un estudio exploratorio, no es necesario clasificar los criterios de valoracion como primarios o secundarios. Estan todos detallados en la seccion E.5.1.

E.5.2.1

Timepoint(s) of evaluation of this end point

As the study is exploratory, it is not necessary to classify endpoints as primary or secondary. All endpoints and timepoints have been detailed in section E.5.1.

Dado que se trata de un estudio exploratorio, no es necesario clasificar los criterios de valoracion como primarios o secundarios. Estan todos detallados en la seccion E.5.1.

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

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)

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

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Cohorts

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

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

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Different Informed Consent Forms have been prepared for the different age ranges (ICF for legal representatives, assent forms, ICF for adults).

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

None

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

2016-06-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-06-10

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

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