Estudio de seguridad de la inmunoglobulina intravenosa (IGIV) posterior a la portoenterostomía en lactantes con atresia biliar (PRIME)
Un ensayo de fase 1/2A de terapia con inmunoglobulina intravenosa (IGIV) después de una portoenterostomía en bebés con atresia biliar
The Children Liver Disease Research and Education Network (ChiLDREN) is conducting a clinical trial to determine the feasibility, acceptability, tolerability and safety profile of IVIG treatment administered to infants after hepatic portoenterostomy (HPE) for biliary atresia, as well as investigate preliminary evidence of activity and explore mechanisms of action.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
In this multicenter prospective phase 1/2A open label trial, the feasibility, tolerability and safety of intravenous immunoglobulin (IVIG) therapy following hepatic portoenterostomy (HPE) will be assessed in 29 infants with biliary atresia (BA), efficacy will be estimated and exploratory mechanistic research studies will be performed. After written consent is obtained from the parent or guardian, the subject will be enrolled and will receive three intravenous doses of IVIG at designated intervals over the first 60 days following HPE and will be followed for 360 days after enrollment. Blood will also be obtained during this study to assess potential mechanisms by which the IVIG may alter or reduce bile duct inflammation and injury and improve bile flow. All infants in this trial will also be treated with standardized doses of other routine standard-of-care treatments for BA during this trial (ursodeoxycholic acid, trimethoprim-sulfamethoxasole, and fat-soluble vitamin supplements). This routine clinical care will not be modified by participation in this study. Subjects in this study will not receive corticosteroid therapy for treatment of biliary atresia, as this is of unproven benefit at the present time.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Ontario
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Toronto, Ontario, Canadá, M5G 1X8
- Hospital for Sick Children
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California
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Los Angeles, California, Estados Unidos, 90027
- Children's Hospital Los Angeles
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Colorado
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Aurora, Colorado, Estados Unidos, 80045
- Children's Hospital Colorado
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Children's Healthcare of Atlanta
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Ohio
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Cincinnati, Ohio, Estados Unidos, 45229
- Children's Hospital Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Estados Unidos, 15213
- Children's Hospital at Pittsburgh
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Infant under 120 days old with established diagnosis of BA. Subjects in this trial must start treatment within 3-5 days of the Kasai procedure and be part of a prospective study of the natural history of biliary atresia also being conducted by ChiLDREN (http://www.clinicaltrials.gov/ct/show/NCT00061828?order=3).
- Standard HPE operation has been performed for BA within the previous 3 days
- Post-conception age ≥ 36 weeks at time of enrollment
- Weight at enrolment ≥ 2000 gm
- Written informed consent to participate in the study obtained within 3 days of completion of HPE.
Exclusion Criteria:
- Laparoscopic HPE or "gall bladder Kasai" (cholecysto-portostomy) surgery was performed
- Biliary atresia splenic malformation syndrome (presence of asplenia, polysplenia or double spleen)
- History of a hypercoagulable disorder
- Renal Disease defined as serum creatinine > 1.0 mg/dl prior to enrollment or presence of complex renal anomalies found on imaging
- Evidence of congestive heart failure or fluid overload
- Presence of significant systemic hypertension for age (defined as persistent systolic blood pressure ≥112 mmHg measured on at least 3 occasions following HPE)
- Infants whose mother is known to have human immunodeficiency virus infection
- Infants whose mother is known to be serum HBsAg or hepatitis C virus antibody positive
- Previous treatment with intravenous immunoglobulin therapy or corticosteroid therapy
- Previous treatment with any other investigational agent
- History of allergic reaction to any human blood product infusion
- Infants with other severe concurrent illnesses, such as neurological, cardiovascular, pulmonary, metabolic, endocrine, and renal disorders, that would interfere with the conduct and results of the study
- Any other clinical condition that is a contraindication to the use of IVIG
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: IVIG active treatment
Intravenous immunoglobulin (IVIG) 10% 1 gm/kg body weight/dose Day 3-5,30, 60 post HPE |
All participants will receive the same dose of IVIG at the same intervals in an open-label fashion as long as the subject does not have any increased risk for toxicity for any IVIG infusion. IVIG will be initiated on day 3 (up to day 5) after HPE surgery (HPE is day 0) at a dose of 1 gm/kg body weight by slow intravenous infusion over at least 4 hours. The same dose (1 gm/kg) and duration of infusion will be repeated on day 30 and day 60 after HPE.
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Feasibility of IVIG Treatment
Periodo de tiempo: 60 days post-HPE
|
Percentage of subjects for whom administration of IVIG is feasible, defined as the successful administration (at least 80% of each dose) of all 3 doses of IVIG |
60 days post-HPE
|
|
Acceptability of IVIG
Periodo de tiempo: 60 days post-HPE
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Percentage of subjects for whom the study is acceptable, defined as the ability of the subject's family or guardian to allow intravenous line placements, blood draws, and other study procedures for the study subjects. |
60 days post-HPE
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|
Serious Adverse Events
Periodo de tiempo: 360 days post-HPE
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Percentage of subjects with any serious adverse events (SAEs) prior to liver transplant |
360 days post-HPE
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|
Level 3-5 Toxicity
Periodo de tiempo: 360 days post-HPE
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Percentage of subjects with any level 3, 4, or 5 toxicity (per NCI CTEP grading system) |
360 days post-HPE
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|
Adverse Events
Periodo de tiempo: 360 days post-HPE
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Percentage of subjects with other expected adverse events |
360 days post-HPE
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Good Bile Drainage at 90 Days Post-HPE
Periodo de tiempo: 90 days post-HPE
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Percentage of subjects who survive 90 days after HPE with both their native liver and serum total bilirubin <1.5 mg/dL at 90 days after HPE |
90 days post-HPE
|
|
Good Bile Drainage at 180 Days Post-HPE
Periodo de tiempo: 180 days post-HPE
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Percentage of subjects who survive 180 days after HPE with both their native liver and serum total bilirubin <1.5 mg/dL at 180 days after HPE |
180 days post-HPE
|
|
Good Bile Drainage at 360 Days Post-HPE
Periodo de tiempo: 360 days post-HPE
|
Percentage of subjects who survive 360 days after HPE with both their native liver and serum total bilirubin <1.5 mg/dL at 360 days after HPE |
360 days post-HPE
|
|
Transplant-free Survival
Periodo de tiempo: 360 days post-HPE
|
Percentage of subjects who survive with their native liver at 360 days after HPE. |
360 days post-HPE
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Circulating Regulatory T-Cells, Inflammatory Cytokines, and Specific Autoantibodies.
Periodo de tiempo: Over 360 days after HPE
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Percentage and absolute number of Tregs (CD4+CD25+FoxP3+), CD3/4 T cells, CD3/8 T cells, NK cells (CD56), NK T cells (CD3/56), CD19/20 B cells, macrophages (CD14/11b), and neutrophils; plasma levels of anti-enolase antibody; and plasma cytokine levels (Th1/Th2 multiplex and IL17) |
Over 360 days after HPE
|
Colaboradores e Investigadores
Investigadores
- Silla de estudio: Ronald Sokol, MD, Children's Hospital Colorado
- Director de estudio: Ed Doo, MD, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)
- Director de estudio: Averell Sherker, MD, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimado)
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
- Enfermedades del Sistema Digestivo
- Enfermedades del Tracto Biliar
- Anomalías congénitas
- Enfermedades de las vías biliares
- Anormalidades del Sistema Digestivo
- Enfermedades y anomalías congénitas, hereditarias y neonatales
- Atresia biliar
- Aminoácidos, péptidos y proteínas
- Proteínas
- Anticuerpos
- Inmunoglobulinas
- Inmunoproteínas
- Proteínas de la sangre
- Globulinas séricas
- Globulinas
- Isotipos de inmunoglobulina
- Inmunoglobulina G
- Inmunoglobulinas Intravenosas
- Hizentra
Otros números de identificación del estudio
- P007 PRIME
- U01DK062456 (Subvención/contrato del NIH de EE. UU.)
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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