A Study to Determine the Optimal Dose of Tildrakizumab (SCH 900222/MK-3222) for the Treatment of Moderate-to-severe Chronic Plaque Psoriasis (P05495) (MK-3222-003)
18 de enero de 2019 actualizado por: Merck Sharp & Dohme LLC
Randomized, Double-Blinded, Placebo-Controlled, Parallel-Design, Dose-Range Finding Study of Subcutaneous Tildrakizumab (SCH 900222/MK-3222) in Subjects With Moderate-to-Severe Chronic Plaque Psoriasis (Study P05495)
This is a response-driven study of tildrakuzumab for the treatment of moderate to severe chronic plaque psoriasis.
The primary study hypothesis is that one or more doses of tildrakizumab will be superior to placebo for the treatment of psoriasis.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
Each participant will be enrolled in the trial for approximately 72-76 weeks.
Each participant will receive assigned treatment at Weeks 0 and 4 in Part I.
At Week 16, the dosage of treatment the patient is assigned to may be adjusted based on the Psoriasis Area and Severity Index (PASI) 75 response (responder vs non-responder).
Participants will receive study medication once every 12 weeks during Part 2 (Weeks 16 to 52); no participants will receive placebo in Part 2. Part 3 is an observational period and each subject will continue to be monitored on a monthly basis through Week 72.
Subjects will not receive any study medication during Part 3.
Tipo de estudio
Intervencionista
Inscripción (Actual)
355
Fase
- Fase 2
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Adult participants (≥18 years of age) with a diagnosis of moderate-to-severe chronic plaque psoriasis (defined by ≥10% body surface area [BSA] involvement, "moderate" or greater score on the Physician's Global Assessment [PGA] scale, and PASI score ≥12 at Baseline)
- Participants must have a diagnosis of predominantly plaque psoriasis for ≥6 months (as determined by interview and confirmation of diagnosis through physical examination by investigator) and be considered candidates for phototherapy or systemic therapy. Participants with psoriatic arthritis may be included in the study
Exclusion Criteria:
- Nonplaque forms of psoriasis specifically erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis
- Participants who will require oral or injectable corticosteroids during the trial
- Presence of any infection requiring treatment with systemic antibiotics within 2 weeks prior to Screening, or serious infection (eg, pneumonia, cellulitis, bone or joint infections) requiring hospitalization or treatment with intravenous antibiotics within 8 weeks prior to Screening
- Participants with evidence of active or untreated latent tuberculosis (TB) according to Screening criteria specified in the protocol. (Prophylactic treatment for latent TB as per local guidelines must be initiated at least 4 weeks prior to treatment with study medication)
- Previous exposure to any agents targeting interleukin-12 (IL-12) and/or Interleukin-23 (IL-23)
- Participants with prior exposure to two or more tumor necrosis factor (TNF) antagonists with discontinuation due to lack of efficacy.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Part 1: Tildrakizumab 5 mg
Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4
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SC administration of tildrakizumab at assigned dose
Otros nombres:
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Experimental: Part 1: Tildrakizumab 25 mg
Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4
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SC administration of tildrakizumab at assigned dose
Otros nombres:
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Experimental: Part 1: Tildrakizumab 100 mg
Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4
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SC administration of tildrakizumab at assigned dose
Otros nombres:
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Experimental: Part 1: Tildrakizumab 200 mg
Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4
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SC administration of tildrakizumab at assigned dose
Otros nombres:
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Comparador de placebos: Part 1: Placebo
Participants receive placebo, SC, at Weeks 0 and 4
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SC administration of Placebo
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Experimental: Part 2: Tildrakizumab 5 mg
Participants receive tildrakizumab 5 mg, SC, every 12 weeks for up to 36 weeks
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SC administration of tildrakizumab at assigned dose
Otros nombres:
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Experimental: Part 2: Tildrakizumab 25 mg
Participants receive tildrakizumab 25 mg, SC, every 12 weeks for up to 36 weeks
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SC administration of tildrakizumab at assigned dose
Otros nombres:
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Experimental: Part 2: Tildrakizumab 100 mg
Participants receive tildrakizumab 100 mg, SC, every 12 weeks for up to 36 weeks
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SC administration of tildrakizumab at assigned dose
Otros nombres:
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Experimental: Part 2: Tildrakizumab 200 mg
Participants receive tildrakizumab 200 mg, SC, every 12 weeks for up to 36 weeks
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SC administration of tildrakizumab at assigned dose
Otros nombres:
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Sin intervención: Part 3: Tildrakizumab 5 mg Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
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Sin intervención: Part 3: Tildrakizumab 25 mg Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
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Sin intervención: Part 3: Tildrakizumab 100 mg Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
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Sin intervención: Part 3: Tildrakizumab 200 mg Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
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Sin intervención: Part 3: Placebo Follow-up
Participants are followed for up to 20 weeks after the last dose of study drug.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Percentage of Participants With a Psoriasis Area and Severity Index (PASI)75 Response at Week 16
Periodo de tiempo: Week 16
|
The PASI score measures the severity and extent of psoriasis.
Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score.
The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score.
Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals.
The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2,
and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).
PASI 75 response was defined as >=75% improvement in PASI score when compared to the baseline score.
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Week 16
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Number of Participants Experiencing Adverse Events
Periodo de tiempo: Up to 72 weeks
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An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
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Up to 72 weeks
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Number of Particpants Discontinuing Study Treatment Due to Adverse Events
Periodo de tiempo: Up to 52 weeks
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An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
Participants may be discontinued from study drug due to adverse events, but remain on the study.
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Up to 52 weeks
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Percentage of Participants With a PASI 75 Response at Week 12
Periodo de tiempo: Week 12
|
The PASI score measures the severity and extent of psoriasis.
Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score.
The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score.
Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals.
The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2,
and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).
PASI 75 response was defined as >=75% improvement in PASI score when compared to the baseline score.
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Week 12
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Percentage of Participants With Physician's Global Assessment (PGA) of "Cleared" or "Minimal" at Week 16
Periodo de tiempo: Week 16
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The PGA is used to determine the overall severity of a subject's psoriasis lesions at a given time point.
Overall lesions will be graded for induration, erythema, and scaling on a scale from 0 to 5. The sum of the 3 scales will be divided by 3 to obtain the PGA score.
PGA is assessed as: 0= Cleared, except for residual discoloration.
1= Minimal, majority of lesions have individual scores that average .
2 =Mild, majority of lesions have individual scores that average 2. 3= Modreate, majority of lesions have individual scores that average 3. 4= Marked, majority of lesions have individual scores that average 4. 5= Severe, majority of lesions have individual scores that average 5.
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Week 16
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Percentage of Participants With PASI 90 Response at Week 16
Periodo de tiempo: Week 16
|
The PASI score measures the severity and extent of psoriasis.
Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score.
The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score.
Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals.
The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2,
and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).
PASI 90 response was defined as >=90 % improvement in PASI score when compared to the baseline score.
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Week 16
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Percentage of Participants With PASI 100 Response at Week 16
Periodo de tiempo: Week 16
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The PASI score measures the severity and extent of psoriasis.
Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score.
The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score.
Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals.
The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2,
and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).
PASI 100 response was defined as 100 % improvement in PASI score when compared to the baseline score.
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Week 16
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PASI 75 Response Rate by Time
Periodo de tiempo: Up to 16 Weeks
|
The PASI score measures the severity and extent of psoriasis.
Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score.
The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score.
Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals.
The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2,
and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).PASI 75 response was defined as >=75% improvement in PASI score when compared to the baseline score at Week 2, 4, 6, 8, 12, or 16.
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Up to 16 Weeks
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Mean Change From Baseline in PASI Score at Weeks 12 and 16
Periodo de tiempo: Baseline and Weeks 12 and 16
|
The PASI score measures the severity and extent of psoriasis.
Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score.
The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score.
Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals.
The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2,
and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).
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Baseline and Weeks 12 and 16
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Percentage of Participants With PASI 50 Response at Week 16
Periodo de tiempo: Week 16
|
The PASI score measures the severity and extent of psoriasis.
Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score.
The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score.
Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals.
The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2,
and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).
PASI 50 response was defined as >=50 % improvement in PASI score when compared to the baseline score.
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Week 16
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Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16
Periodo de tiempo: Week 16
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The DLQI is a 10-item questionnaire that measures how much participant skin problems have affected their life.
Responses range from 0=Not at all to 3=Very much.
The DLQI is broken down into 6 subscales: Symptoms and feelings (range 0-6), Daily activities (range 0-6), Leisure (range 0-6), Work and school (range 0-3), Personal relationships (range 0-6), and Treatment (range 0-3).
DLQI subscales were summed to yield the DLQI total score, which could range from 0 to 30.
For both DLQI subscales and DLQI total score, a higher score indicated a greater negative impact on life.
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Week 16
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Percentage of Participants Achieving DLQI Score of 0 or 1 at Week 16
Periodo de tiempo: Week 16
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The DLQI is a 10-item questionnaire that measures how much participant skin problems have affected their life.
Responses range from 0=Not at all to 3=Very much.
The DLQI is broken down into 6 subscales: Symptoms and feelings (range 0-6), Daily activities (range 0-6), Leisure (range 0-6), Work and school (range 0-3), Personal relationships (range 0-6), and Treatment (range 0-3).
DLQI subscales were summed to yield the DLQI total score, which could range from 0 to 30.
For both DLQI subscales and DLQI total score, a higher score indicated a greater negative impact on life.
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Week 16
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Percentage of Participants Achieving a >=5 Point Reduction in DLQI at Week 16
Periodo de tiempo: Week 16
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The DLQI is a 10-item questionnaire that measures how much participant skin problems have affected their life.
Responses range from 0=Not at all to 3=Very much.
The DLQI is broken down into 6 subscales: Symptoms and feelings (range 0-6), Daily activities (range 0-6), Leisure (range 0-6), Work and school (range 0-3), Personal relationships (range 0-6), and Treatment (range 0-3).
DLQI subscales were summed to yield the DLQI total score, which could range from 0 to 30.
For both DLQI subscales and DLQI total score, a higher score indicated a greater negative impact on life.
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Week 16
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- Kerbusch T, Li H, Wada R, Jauslin PM, Wenning L. Exposure-response characterisation of tildrakizumab in chronic plaque psoriasis: Pooled analysis of 3 randomised controlled trials. Br J Clin Pharmacol. 2020 Sep;86(9):1795-1806. doi: 10.1111/bcp.14280. Epub 2020 Mar 25.
- Jauslin P, Kulkarni P, Li H, Vatakuti S, Hussain A, Wenning L, Kerbusch T. Population-Pharmacokinetic Modeling of Tildrakizumab (MK-3222), an Anti-Interleukin-23-p19 Monoclonal Antibody, in Healthy Volunteers and Subjects with Psoriasis. Clin Pharmacokinet. 2019 Aug;58(8):1059-1068. doi: 10.1007/s40262-019-00743-7.
- Papp K, Thaci D, Reich K, Riedl E, Langley RG, Krueger JG, Gottlieb AB, Nakagawa H, Bowman EP, Mehta A, Li Q, Zhou Y, Shames R. Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015 Oct;173(4):930-9. doi: 10.1111/bjd.13932. Epub 2015 Oct 15. Erratum In: Br J Dermatol. 2016 Jun;174(6):1426.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
25 de octubre de 2010
Finalización primaria (Actual)
4 de noviembre de 2011
Finalización del estudio (Actual)
24 de octubre de 2012
Fechas de registro del estudio
Enviado por primera vez
7 de octubre de 2010
Primero enviado que cumplió con los criterios de control de calidad
20 de octubre de 2010
Publicado por primera vez (Estimar)
21 de octubre de 2010
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
5 de febrero de 2019
Última actualización enviada que cumplió con los criterios de control de calidad
18 de enero de 2019
Última verificación
1 de enero de 2019
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- P05495
- 2009-017272-24 (Número EudraCT)
- MK-3222-003 (Otro identificador: Merck Research Laboratories)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
SÍ
Descripción del plan IPD
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Datos del estudio/Documentos
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .