| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10047642 |
| E.1.2 | Term | Vitiligo |
| E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the efficacy of ruxolitinib cream in participants with vitiligo. |
| Evaluar la eficacia de la crema de ruxolitinib en participantes con vitíligo |
|
| E.2.2 | Secondary objectives of the trial |
Key secondary:
To further assess the efficacy of ruxolitinib cream
Secondary:
To evaluate the safety and tolerability of ruxolitinib cream.
To evaluate the ruxolitinib PK in plasma after treatment of ruxolitinib cream. |
Secundarios clave
Adicionalmente la eficacia de la crema de ruxolitinib.
Secundarios:
Evaluar la seguridad y tolerabilidad de la crema de ruxolitinib.
Evaluar la PK de ruxolitinib en plasma después del tratamiento con crema de ruxolitinib |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Adolescents and adults aged ≥ 12 years.
2. Participants with a clinical diagnosis of non-segmental vitiligo with depigmented area including ≥ 0.5% BSA on the face, ≥ 0.5 F-VASI, ≥ 3% BSA on nonfacial areas, ≥ 3 T-VASI, and total body vitiligo area (facial and nonfacial) not exceeding 10% BSA.
3. Participants who agree to discontinue all agents used to treat vitiligo from screening through the final safety follow-up visit. Over-the-counter preparations deemed acceptable by the investigator and camouflage makeups are permitted.
4. Male and female participants must be willing to take appropriate contraceptive measures to avoid pregnancy or fathering a child for the duration of study participation with the exception of the following:
a. Females of non-childbearing potential (ie, or surgically sterile with a hysterectomy and/or bilateral oophorectomy OR postmenopausal, ≥ 12 months of amenorrhea without an alternative medical cause).
b. Prepubescent adolescents.
Note: Information about specific types of acceptable contraceptive measures and duration of contraceptive use are provided in the protocol.
5. For adult participant, ability to comprehend and willingness to sign an ICF, for adolescent participant written informed consent of the parent(s) or legal guardian and written assent from the adolescent participant.
Note: Adolescents, who during the course of the study become legal adults, will be asked for their consent to continue the study, and in the event of lack thereof, will be discontinued from further participation. |
1. Adolescentes y adultos de edad ≥ 12 años.
2. Participantes con diagnóstico clínico de vitiligo no segmentario con área despigmentada que incluye ≥ 0.5% de BSA en la cara, ≥ 0.5 F-VASI, ≥ 3% de BSA en áreas no faciales, ≥ 3 T-VASI y área de vitiligo corporal total ( facial y no facial) que no exceda el 10% de BSA.
3. Participantes que aceptan suspender todos los agentes utilizados para tratar el vitiligo desde el cribado hasta la visita de seguimiento de seguridad final. Se permiten preparaciones de venta libre consideradas aceptables por el investigador y maquillajes de camuflaje.
4. Los participantes masculinos y femeninos deben estar dispuestos a tomar las medidas anticonceptivas apropiadas para evitar el embarazo o la maternidad de un hijo durante la participación en el estudio, con la excepción de lo siguiente:
a. Mujeres de potencial no reproductivo (es decir, o quirúrgicamente estériles con una histerectomía y / o ooforectomía bilateral O posmenopáusica, ≥ 12 meses de amenorrea sin una causa médica alternativa).
si. Adolescentes prepúberes.
Nota: En el protocolo se proporciona información sobre tipos específicos de medidas anticonceptivas aceptables y la duración del uso de anticonceptivos.
5. Para el participante adulto, la capacidad de comprender y la voluntad de firmar un ICF, para el consentimiento informado por escrito del participante adolescente del padre (s) o tutor legal y el consentimiento por escrito del participante adolescente.
Nota: A los adolescentes, que durante el curso del estudio se convierten en adultos legales, se les pedirá su consentimiento para continuar el estudio y, en caso de falta del mismo, se les suspenderá su participación. |
|
| E.4 | Principal exclusion criteria |
1. Participants who have no pigmented hair within any of the vitiligo areas on the face.
2. Other forms of vitiligo (eg, segmental) or other differential diagnosis of vitiligo or other skin depigmentation disorders (eg, piebaldism, pityriasis alba, leprosy, postinflammatory hypopigmentation, progressive macule hypomelanosis, nevus anemicus, chemical leukoderma, and tinea versicolor).
3. Participants who have used depigmentation treatments (eg, monobenzone) for past treatment of vitiligo or other pigmented areas.
Note: Prior use of hydroquinone is not prohibited (as it is a bleaching agent, not a depigmentation treatment).
4. Participants with concurrent conditions and history of other diseases:
a. Any other skin disease that, in the opinion of the investigator, would interfere with the study medication application or study assessments.
b. Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes zoster, chicken pox) within 1 week before baseline.
c. Conditions at baseline that would interfere with evaluation of vitiligo.
d. Any serious illness or medical, physical, or psychiatric condition(s) that, in the investigator's opinion, would interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
Examples include but are not limited to the following:
− Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy or uncontrolled hypertension (blood pressure > 150/90 mmHg) unless approved by the medical monitor/sponsor.
− History of thrombosis, including deep venous thrombosis and pulmonary embolism.
− Participants with concurrent malignant disease or a history of that in the 5 years preceding the baseline visit except for adequately treated nonmetastatic malignancies.
− Current and/or history of liver disease, including known hepatitis B or C, with hepatic or biliary abnormalities.
− History of alcoholism or drug addiction within 1 year before screening or current alcohol or drug use that, in the opinion of the investigator, will interfere with the participant's ability to comply with the administration schedule and study assessments.
− Participants who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
5. Participants using any of the following treatments within the indicated washout period before baseline:
a. 1 week: Topical drugs when used on the vitiligo areas, for example, corticosteroids, calcineurin, and phosphodiesterase type 4 inhibitors or retinoids.
b. 4 weeks:
− Melanocyte-stimulating agents (eg, afamelanotide).
− Immunomodulating systemic medications (eg, corticosteroids, methotrexate, cyclosporine).
− Any other systemic therapies that could increase the skin sensitivity to UV/visible light or impact skin pigmentation, for example, tetracyclines, metoxypsoralens.
− Received live vaccine.
Note: Live vaccine is prohibited during the course of the study and within 4 weeks after the EOT visit.
c. 8 weeks: Laser or any kind of phototherapy, including tanning bed or intentional UV exposure.
d. 5 half-lives or 12 weeks, whichever is longer: Biologic agents, investigational or experimental therapy or procedures for vitiligo. Investigational biologics should be discussed with the sponsor to determine whether a longer period of discontinuation is required.
6. Participants who have previously received JAK inhibitors, systemic or topical.
7. Participants with clinically significant abnormal laboratory values at screening:
a. Hemoglobin (< 10 g/dL).
b. Liver function tests:
− AST or ALT ≥ 2 × ULN.
− Alkaline phosphatase and/or bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%).
c. Severe renal disease (with creatinine clearance < 30 ml/min) or renal disease requiring dialysis.
d. Clinically significant abnormal TSH or free T4 at screening as determined by the investigator.
e. Positive serology test results at screening for HIV antibody.
8. Body mass index < 17 or > 40 kg/m2.
9. Pregnant or lactating participants, or those considering pregnancy during the period of their study participation.
10. Participants who, in the opinion of the investigator, are unable or unlikely to comply with the administration schedule and study evaluations.
11. Employees of the sponsor or investigator or are otherwise dependents of them.
12. Participants with known allergy or reaction to any component of the study formulation |
1. Participantes que no tienen cabello pigmentado en ninguna de las áreas de vitiligo en la cara.
2. Otras formas de vitiligo (p. Ej., Segmentario) u otro diagnóstico diferencial de vitiligo u otros trastornos de despigmentación de la piel (p. Ej., Piebaldismo, pitiriasis alba, lepra, hipopigmentación postinflamatoria, hipomelanosis macular progresiva, nevo anémico, leucodermia química y tiña versicolor).
3. Participantes que han usado tratamientos de despigmentación (p. Ej., Monobenzona) para tratamientos anteriores de vitiligo u otras áreas pigmentadas.
Uso previo de hidroquinona no está prohibido
4. Participantes con condiciones concurrentes y antecedentes de otras enfermedades:
a. Cualquier otra enfermedad de la piel q segun el investigador, interferiría con la aplicación de la medicación o evaluaciones del estudio
b. Infección cutánea aguda bacteriana, fúngica o viral activa Pej.Herpes simple o zoster, varicela) la semana anterior al inicio.
c. Condiciones al inicio del estudio que interferirían con la evaluación del vitiligo.
d.Enfermedad grave o afecciones médicas, físicas o psiquiátricas q según el investigador, interferirían con la plena participación en el estudio, incluida la administración del medicamento y la asistencia a las visitas requeridas; plantear riesgo significativo para participante, interferir con interpretación de los datos del estudio.
Enfermedad cardíaca clínicamente no controlada, angina infarto agudo de miocardio en 6 meses posteriores al día 1 de la administración del fármaco, insuficiencia cardíaca congestiva de clase III o IV arritmia que requiere tratamiento,hipertensión no controlada (PA> 150 / 90 mmHg) a no ser que lo apruebe el sponor
- Historia de trombosis, incluyendo trombosis venosa profunda y embolia pulmonar.
- Participantes con enfermedad maligna concurrente o antecedentes de la misma en los 5 años anteriores a la visita basal, excepto por malignidades no metastásicas tratadas adecuadamente.
- Actualidad/antecedentes de enfermedad hepática, incluida la hepatitis B o C conocida, con anomalías hepáticas o biliares.
- Historial de alcoholismo, drogas dentro de 1 año antes de la detección o el uso actual de alcohol o drogas que, segun investigador, interferirá con la capacidad del participante para cumplir con el cronograma de administración y las evaluaciones del estudio.
- Participantes comprometidos con una institución en virtud de una orden emitida por las autoridades judiciales o administrativas.
Participantes que usan cualquiera de los siguientes tratamientos dentro del período de lavado indicado antes del inicio del estudio:
a. 1 semana: medicamentos tópicos cuando se usan en las áreas de vitiligo, por ejemplo, corticosteroides, calcineurina e inhibidores de la fosfodiesterasa tipo 4 o retinoides.
si. 4 semanas:
- Agentes estimuladores de melanocitos
- Medicamentos sistémicos inmunomoduladores
- Cualquier terapia sistémica que pueda aumentar la sensibilidad de la piel a los rayos UV / luz visible o afectar la pigmentación de la piel, por ejemplo, tetraciclinas, metoxipsoralenos.
- Recibir la vacuna viva.
Nota: La vacuna viva está prohibida durante el transcurso del estudio y dentro de las 4 semanas posteriores a la visita del EOT.
do. 8 semanas: láser o cualquier tipo de fototerapia, incluida la cama de bronceado o la exposición intencional a los rayos UV.
re. 5 semividas o 12 semanas, lo que sea más largo: agentes biológicos, terapia experimental o experimental o procedimientos para el vitiligo. Los productos biológicos de investigación deben discutirse con el patrocinador para determinar si se requiere un período de interrupción más prolongado.
6. Participantes que hayan recibido previamente inhibidores de JAK, sistémicos o tópicos.
7. Participantes con valores de laboratorio anormales clínicamente significativos en el cribado:
a. Hemoglobina (<10 g / dL).
si. Pruebas de función hepática:
- AST o ALT ≥ 2 × ULN.
- Fosfatasa alcalina y / o bilirrubina> 1.5 × ULN (la bilirrubina aislada> 1.5 × ULN es aceptable si la bilirrubina está fraccionada y la bilirrubina directa <35%).
do. Enfermedad renal grave (con aclaramiento de creatinina <30 ml / min) o enfermedad renal que requiere diálisis.
re. TSH anormal clínicamente significativa o T4 libre en el cribado según lo determine el investigador.
mi. Resultados positivos de la prueba serológica en la detección de anticuerpos contra el VIH.
8. Índice de masa corporal <17 o> 40 kg / m2.
9. Participantes embarazadas o lactantes, o aquellas que estén considerando un embarazo durante el período de su participación en el estudio.
10. Participantes que, en opinión del investigador, no pueden o no pueden cumplir con el cronograma de administración y las evaluaciones del estudio.
11. Empleados del patrocinador o investigador o que sean dependientes de ellos.
12. Participantes con alergia o reacción conocida a cualquier componente de la formulación del estudio. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of participants achieving F-VASI75 at Week 24. |
| Proporción de participantes que logran F-VASI75 en la semana 24 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Key secondary:
• Percentage change from baseline in F-BSA at Week 24.
• Proportion of participants achieving F-VASI50 at Week 24.
• Proportion of participants achieving F-VASI75 at Week 52.
• Proportion of participants achieving F-VASI90 at Week 24.
• Proportion of participants achieving F-VASI90 at Week 52.
• Proportion of participants achieving T-VASI50 at Week 24.
• Proportion of participants achieving T-VASI50 at Week 52.
• Proportion of participants achieving T-VASI75 at Week 52.
• Proportion of participants achieving a VNS of “4 – A lot less noticeable” or “5 – No longer noticeable” at Week 24.
Secondary:
• The frequency, duration, and severity of AEs; physical examinations; vital signs; and laboratory data for hematology and serum chemistry.
• Proportion of participants achieving F-VASI25/50/75/90 during the treatment period (double-blind and treatment extension periods).
• Percentage change from baseline in F-VASI during the treatment period (double-blind and treatment extension periods).
• Percentage change from baseline in F-BSA during the treatment period (double-blind and treatment extension periods).
• Percentage change from baseline in T-VASI during the treatment period (double-blind and treatment extension periods).
• Percentage change from baseline in T-BSA during the treatment period (double-blind and treatment extension periods).
• Proportion of participants achieving T-VASI25/50/75/90 during the treatment period (double-blind and treatment extension periods).
• Proportion of participants in each category of VNS during the treatment period (double-blind and treatment extension periods).
• Population-based (trough) plasma concentrations of ruxolitinib at Weeks 4, 24 and 40. |
Cambio porcentual desde el inicio en el ASC-F en la semana 24.
Proporción de participantes que logran F-VASI50 en la semana 24
Proporción de participantes que logran F-VASI75 en la semana 52
Proporción de participantes que logran F-VASI90 en la semana 24
Proporción de participantes que logran F-VASI90 en la semana 52
Proporción de participantes que logran T-VASI50 en la semana 24
Proporción de participantes que logran T-VASI50 en la semana 52
Proporción de participantes que logran T-VASI75 en la semana 52
Proporción de participantes que logra una VNS de “4 – mucho menos notorio” o “5 - no más notorio” en la semana 24.
La frecuencia, duración e intensidad de los AA; exploraciones físicas; constantes vitales; y datos de laboratorio para hematología y bioquímica sérica.
Proporción de pacientes que logran F-VASI25/50/75/90 durante el período de tratamiento (períodos doble ciego y extensión de tratamiento).
Proporción de pacientes que logran T-VASI25/50/75/90 durante el período de tratamiento (períodos doble ciego y extensión de tratamiento).
Proporción de pacientes en cada categoría de la VNS durante el período de tratamiento (períodos doble ciego y extensión de tratamiento).
Concentraciones plasmáticas (mínimas) de ruxolitinib en la población en las semanas 4, 24 y 40. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 4, 24 , 40 and 52 weeks |
| Semanas 4, 24,40 y 52 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| To determine the participants’ quality of life. |
| Determinar la calidad de vida de los pacientes |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 32 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Bulgaria |
| Canada |
| France |
| Germany |
| Italy |
| Netherlands |
| Poland |
| Spain |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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 |
| Ultima Visita del Ultimo Paciente |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| 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 | 2 |
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