- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT07583745
Study of EPN-701 for the Treatment of Calciphylaxis
Phase 2 Study of EPN-701 for the Treatment of Calciphylaxis
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
This is a phase 2 double-blind RCT that will randomly assign 60 adult dialysis-dependent patients with calciphylaxis to either EPN-701 (10 mg/day administered orally) or a matched placebo in a 1:1 ratio for 24 weeks. Standardized background clinical care will be applied to all participants.
Primary objective will be to determine the clinical efficacy and safety of EPN-701 in dialysis-dependent patients with calciphylaxis. The clinical efficacy will be assessed by pre-post (Baseline-Week 24) change in pain intensity and calciphylaxis wound surface area.
Secondary objective will be to examine the safety of EPN-701 in dialysis-dependent patients with calciphylaxis. Safety will be assessed by active monitoring for adverse events throughout the trial period.
The pharmacodynamic efficacy will be primarily assessed by pre-post (Baseline-Week 12) change in plasma ucMGP among the trial arms. EPN-701 plasma concentration time profiles and other pharmacokinetic assessments will also be assessed.
Exploratory outcomes will be pre-post (Baseline-Week 24) changes in radiotracer uptake indicative of calcification burden, wound severity scores, hospitalization, mortality, and quality of life. The Investigators will also explore novel biomarkers of calciphylaxis via plasma proteomics and examine the associations between changes in ucMGP, radiotracer uptake, and novel biomarkers with patient-oriented clinical outcomes to inform the selection of efficacy endpoints for a future phase 3 RCT.
Findings from the proposed trial will inform the end point selection and design of a future phase 3 trial aimed at establishing a targeted novel therapy for calciphylaxis.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02114
- Renal Associates
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Contacto:
- Scott Krinsky
- Número de teléfono: 9784063408
- Correo electrónico: skrinsky1@mgb.org
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Contacto:
- Correo electrónico: skrinsky1@mgb.org
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-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Participant must provide written or electronic consent after the nature of the study has been explained, and prior to any research-related procedures, per the International Conference on Harmonization (ICH) Good Clinical Practice (GCP)
- Clinical diagnosis of calciphylaxis confirmed by the Investigator with presence of at least one ulcerated skin lesion and moderate or severe pain (worst pain intensity in the preceding 24 hours of at least 5 on a 0-10 scale). Consistent with the clinical practice and expert recommendations, histological confirmation of calciphylaxis diagnosis by a skin biopsy is not a requirement for participation.
- ESKD requiring thrice weekly hemodialysis
- Male or female aged ≥18 years
- Women of childbearing potential (WOCBP) as defined in Clinical Trials Facilitation and Coordination Group (CTFG, 2020) must have a negative serum pregnancy test (defined as serum hCG ≤25 mIU/mL [Haninger-Vacariu, 2020]) at Screening
- Women of childbearing potential (WOCBP) must be using or agree to use one highly effective form of contraception and a barrier method from Screening through 30 days after the last dose of study treatment. See Appendix C for further information about highly effective forms of contraception.
- Males who are sexually active must agree to use condoms from the period following first dose of study treatment through four weeks after the last dose of study treatment. Males with a WOCBP partner must agree to use one highly effective form of contraception in addition to condoms from Screening through 30 days after the last dose of study treatment.
- Males must agree to not donate sperm from the period following the first dose of study treatment through 4 weeks after last dose of study treatment. WOCBP who are participants or partners of fertile male participants must agree not to donate ova from the period following the first dose of study treatment through 4 weeks after last dose of study treatment.
Exclusion Criteria:
- In the opinion of the Investigator, presence of any clinically significant disease outside of calciphylaxis that may impact study participation and/or confound interpretation of the study results
- Hospitalized at the time of Screening. Patients discharged from a hospital admission ≥24 hours prior to Screening may be eligible for participation.
- Septic shock
- Hospice or comfort care including withdrawal from dialysis
- Malignancy within the last year, except non-melanoma skin cancers, cervical carcinoma in situ, or localized prostate cancer.
- Concurrent participation in another interventional clinical study and/or receipt of any other investigational new drug within four weeks prior to the first dose of study treatment, or use of an investigational device, through completion of participation in the study
- Previous participation in a study of EPN-701
- Participants who are pregnant, trying to become pregnant, or breastfeeding
- Participants who are trying to father a child
- Peritoneal dialysis participants
- Kidney transplant recipients who are receiving immunosuppression at the time of Screening and patients who have an imminent transplant plan. Patients who have received a kidney transplant that has failed, necessitating dialysis, and who are no longer on immunosuppression may participate.
- History of or current diagnosis of cirrhosis
- Current use of prohibited medications, including vitamin K-containing medications and warfarin. Patients who have discontinued warfarin treatment upon the diagnosis of calciphylaxis will be eligible for Screening.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Comparador activo: EPN-701
EPN-701 will be administered daily by mouth
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Randomized subjects will receive EPN-701 or placebo
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Comparador de placebos: Placebo
Placebo will be taken daily by mouth
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Randomized subjects will receive EPN-701 or placebo.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in pain intensity (Alternate Primary Endpoint)
Periodo de tiempo: Baseline-24 weeks
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Pre-post (Baseline-Week 24) change in the worst calciphylaxis associated pain intensity as measured on the 0 to 10 scale among the trial arms.
Score of 0 indicates no pain.
Score of 10 indicates most severe pain
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Baseline-24 weeks
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Change in total calciphylaxis lesion(s) surface area (Alternate Primary Endpoint)
Periodo de tiempo: Baseline-24 weeks
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Pre-post (Baseline-Week 24) change in total surface area of ulcerated skin lesions of calciphylaxis among the trial arms
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Baseline-24 weeks
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Plasma level of uncarboxylated matrix Gla protein (uc-MGP)
Periodo de tiempo: Baseline-24 weeks
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Pre-post (Baseline-Week 24) change in plasma uncarboxylated matrix Gla protein (uc-MGP) among the trial arms
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Baseline-24 weeks
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Change in calcification burden
Periodo de tiempo: Baseline-24 weeks
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Pre-post (Baseline-Week 24) change in radiotracer uptake on 18-sodium fluoride positron emission tomography/computerized tomography (18F-NaF PET/CT)
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Baseline-24 weeks
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Changes in additional biomarkers and plasma proteomic
Periodo de tiempo: Baseline-24 weeks
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Pre-post (Baseline-Week 24) changes in biomarkers such as plasma Protein induced by vitamin K absence or antagonist-II (PIVKA- II), fetuin A, and novel markers identified via plasma proteomic analyses
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Baseline-24 weeks
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Change in pain interference
Periodo de tiempo: Baseline-24 weeks
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Pre-post (Baseline-Week 24) change in the pain interference score recorded on Brief Pain Inventory/Short Form (BPI/SF).
Score of 0 indicates no pain interference.
Score of 10 indicates most severe pain interference.
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Baseline-24 weeks
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Change in wound Quality of Life
Periodo de tiempo: Baseline-24 weeks
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Pre-post (Baseline-Week 24) score on Wound QOL.
Scores range from 0 to 4. A lower score indicates better quality of life (0=not at all impaired, 4=very much impaired.
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Baseline-24 weeks
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EPN-701 plasma concentration
Periodo de tiempo: Baseline-24 weeks
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EPN-701 plasma concentration
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Baseline-24 weeks
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Rates of clinical events
Periodo de tiempo: Baseline-24 weeks
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Calciphylaxis associated hospitalization, mortality, infection, or new lesion development
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Baseline-24 weeks
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 2026P000834
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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