Sikkerhetsstudie av intravenøs immunoglobulin (IVIG) post-portoenterostomi hos spedbarn med biliær atresi (PRIME)
En fase 1/2A-forsøk med intravenøs immunoglobulin (IVIG) terapi etter portenterostomi hos spedbarn med biliær atresi
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.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Registrering (Faktiske)
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Studiesteder
-
-
Ontario
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Toronto, Ontario, Canada, M5G 1X8
- Hospital for Sick Children
-
-
-
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California
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Los Angeles, California, Forente stater, 90027
- Children's Hospital Los Angeles
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Colorado
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Aurora, Colorado, Forente stater, 80045
- Children's Hospital Colorado
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Georgia
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Atlanta, Georgia, Forente stater, 30322
- Children's Healthcare of Atlanta
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Ohio
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Cincinnati, Ohio, Forente stater, 45229
- Children's Hospital Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Forente stater, 19104
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Forente stater, 15213
- Children's Hospital at Pittsburgh
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-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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.
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Feasibility of IVIG Treatment
Tidsramme: 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
Tidsramme: 60 days post-HPE
|
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
|
|
Serious Adverse Events
Tidsramme: 360 days post-HPE
|
Percentage of subjects with any serious adverse events (SAEs) prior to liver transplant |
360 days post-HPE
|
|
Level 3-5 Toxicity
Tidsramme: 360 days post-HPE
|
Percentage of subjects with any level 3, 4, or 5 toxicity (per NCI CTEP grading system) |
360 days post-HPE
|
|
Adverse Events
Tidsramme: 360 days post-HPE
|
Percentage of subjects with other expected adverse events |
360 days post-HPE
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Good Bile Drainage at 90 Days Post-HPE
Tidsramme: 90 days post-HPE
|
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
Tidsramme: 180 days post-HPE
|
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
Tidsramme: 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
Tidsramme: 360 days post-HPE
|
Percentage of subjects who survive with their native liver at 360 days after HPE. |
360 days post-HPE
|
|
Circulating Regulatory T-Cells, Inflammatory Cytokines, and Specific Autoantibodies.
Tidsramme: Over 360 days after HPE
|
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
|
Samarbeidspartnere og etterforskere
Etterforskere
- Studiestol: Ronald Sokol, MD, Children's Hospital Colorado
- Studieleder: Ed Doo, MD, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)
- Studieleder: Averell Sherker, MD, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)
Publikasjoner og nyttige lenker
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Antatt)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Sykdommer i fordøyelsessystemet
- Galleveissykdommer
- Medfødte abnormiteter
- Galleveissykdommer
- Abnormiteter i fordøyelsessystemet
- Medfødte, arvelige og neonatale sykdommer og abnormiteter
- Biliær atresi
- Aminosyrer, peptider og proteiner
- Proteiner
- Antistoffer
- Immunoglobuliner
- Immunoproteiner
- Blodproteiner
- Serumglobuliner
- Globuliner
- Immunoglobulinisotyper
- Immunoglobulin G.
- Immunglobuliner, intravenøst
- Hizentra
Andre studie-ID-numre
- P007 PRIME
- U01DK062456 (U.S. NIH-stipend/kontrakt)
Legemiddel- og utstyrsinformasjon, studiedokumenter
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