Trial Outcomes & Findings for Safety Study of Intravenous Immunoglobulin (IVIG) Post-Portoenterostomy in Infants With Biliary Atresia (NCT NCT01854827)
NCT ID: NCT01854827
Last Updated: 2019-10-01
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
30 participants
Primary outcome timeframe
60 days post-HPE
Results posted on
2019-10-01
Participant Flow
Participant milestones
| Measure |
IVIG Active Treatment
Intravenous immunoglobulin (IVIG) 10% 1 gm/kg body weight/dose Day 3-5,30, 60 post HPE
Intravenous immunoglobulin (IVIG): 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.
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|---|---|
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Overall Study
STARTED
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30
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Overall Study
COMPLETED
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29
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Overall Study
NOT COMPLETED
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1
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Reasons for withdrawal
| Measure |
IVIG Active Treatment
Intravenous immunoglobulin (IVIG) 10% 1 gm/kg body weight/dose Day 3-5,30, 60 post HPE
Intravenous immunoglobulin (IVIG): 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.
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|---|---|
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Overall Study
Death
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1
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Baseline Characteristics
Safety Study of Intravenous Immunoglobulin (IVIG) Post-Portoenterostomy in Infants With Biliary Atresia
Baseline characteristics by cohort
| Measure |
IVIG Active Treatment
n=29 Participants
Intravenous Immunoglobulin (IVIG) active treatment for infants with biliary atresia
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|---|---|
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Age, Continuous
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60.0 Days
STANDARD_DEVIATION 18.6 • n=5 Participants
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Sex: Female, Male
Female
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18 Participants
n=5 Participants
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Sex: Female, Male
Male
|
11 Participants
n=5 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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|
Race (NIH/OMB)
Asian
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2 Participants
n=5 Participants
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|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Black or African American
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3 Participants
n=5 Participants
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Race (NIH/OMB)
White
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22 Participants
n=5 Participants
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Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Hispanic
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9 Participants
n=5 Participants
|
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Race/Ethnicity, Customized
Ethnicity · Non-Hispanic
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20 Participants
n=5 Participants
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Region of Enrollment
Canada
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7 Participants
n=5 Participants
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Region of Enrollment
United States
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22 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: 60 days post-HPEPopulation: MITT
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
Outcome measures
| Measure |
IVIG Active Treatment
n=29 Participants
Intravenous Immunoglobulin (IVIG) active treatment for infants with biliary atresia
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|---|---|
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Feasibility of IVIG Treatment
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23 Participants
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PRIMARY outcome
Timeframe: 60 days post-HPEPopulation: MITT
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.
Outcome measures
| Measure |
IVIG Active Treatment
n=29 Participants
Intravenous Immunoglobulin (IVIG) active treatment for infants with biliary atresia
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|---|---|
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Acceptability of IVIG
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23 Participants
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PRIMARY outcome
Timeframe: 360 days post-HPEPopulation: mITT
Percentage of subjects with any serious adverse events (SAEs) prior to liver transplant
Outcome measures
| Measure |
IVIG Active Treatment
n=29 Participants
Intravenous Immunoglobulin (IVIG) active treatment for infants with biliary atresia
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|---|---|
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Serious Adverse Events
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26 Participants
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PRIMARY outcome
Timeframe: 360 days post-HPEPopulation: mITT
Percentage of subjects with any level 3, 4, or 5 toxicity (per NCI CTEP grading system)
Outcome measures
| Measure |
IVIG Active Treatment
n=29 Participants
Intravenous Immunoglobulin (IVIG) active treatment for infants with biliary atresia
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|---|---|
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Level 3-5 Toxicity
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26 Participants
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PRIMARY outcome
Timeframe: 360 days post-HPEPopulation: mITT
Percentage of subjects with other expected adverse events
Outcome measures
| Measure |
IVIG Active Treatment
n=29 Participants
Intravenous Immunoglobulin (IVIG) active treatment for infants with biliary atresia
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|---|---|
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Adverse Events
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8 Participants
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SECONDARY outcome
Timeframe: 90 days post-HPEPopulation: mITT
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
Outcome measures
| Measure |
IVIG Active Treatment
n=29 Participants
Intravenous Immunoglobulin (IVIG) active treatment for infants with biliary atresia
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|---|---|
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Good Bile Drainage at 90 Days Post-HPE
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11 Participants
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SECONDARY outcome
Timeframe: 180 days post-HPEPopulation: mITT
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
Outcome measures
| Measure |
IVIG Active Treatment
n=29 Participants
Intravenous Immunoglobulin (IVIG) active treatment for infants with biliary atresia
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|---|---|
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Good Bile Drainage at 180 Days Post-HPE
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14 Participants
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SECONDARY outcome
Timeframe: 360 days post-HPEPopulation: mITT
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
Outcome measures
| Measure |
IVIG Active Treatment
n=29 Participants
Intravenous Immunoglobulin (IVIG) active treatment for infants with biliary atresia
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|---|---|
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Good Bile Drainage at 360 Days Post-HPE
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7 Participants
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SECONDARY outcome
Timeframe: 360 days post-HPEPopulation: mITT
Percentage of subjects who survive with their native liver at 360 days after HPE.
Outcome measures
| Measure |
IVIG Active Treatment
n=29 Participants
Intravenous Immunoglobulin (IVIG) active treatment for infants with biliary atresia
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|---|---|
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Transplant-free Survival
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17 Participants
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SECONDARY outcome
Timeframe: Over 360 days after HPEPercentage 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)
Outcome measures
Outcome data not reported
Adverse Events
IVIG Active Treatment
Serious events: 26 serious events
Other events: 29 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
IVIG Active Treatment
n=29 participants at risk
Intravenous Immunoglobulin (IVIG) active treatment for infants with biliary atresia
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|---|---|
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Blood and lymphatic system disorders
Anemia
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3.4%
1/29 • Number of events 1 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Gastrointestinal disorders
Gastrointestinal
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10.3%
3/29 • Number of events 3 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Hepatobiliary disorders
Hepatic
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41.4%
12/29 • Number of events 20 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Immune system disorders
Immunological
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10.3%
3/29 • Number of events 3 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Infections and infestations
Infectious
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72.4%
21/29 • Number of events 63 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Metabolism and nutrition disorders
Metabolic
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3.4%
1/29 • Number of events 1 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplastic
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3.4%
1/29 • Number of events 2 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Metabolism and nutrition disorders
Nutritional
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34.5%
10/29 • Number of events 13 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Surgical and medical procedures
Surgical
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6.9%
2/29 • Number of events 2 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Surgical and medical procedures
Post Operative Liver Transplant
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41.4%
12/29 • Number of events 12 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Other adverse events
| Measure |
IVIG Active Treatment
n=29 participants at risk
Intravenous Immunoglobulin (IVIG) active treatment for infants with biliary atresia
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|---|---|
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Renal and urinary disorders
Constipation
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13.8%
4/29 • Number of events 6 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Renal and urinary disorders
Acholic Stools
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48.3%
14/29 • Number of events 22 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Respiratory, thoracic and mediastinal disorders
Allergic Reaction
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3.4%
1/29 • Number of events 2 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Respiratory, thoracic and mediastinal disorders
Allergic Rhinitis
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3.4%
1/29 • Number of events 2 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Blood and lymphatic system disorders
Anemia
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17.2%
5/29 • Number of events 8 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Hepatobiliary disorders
Ascites
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55.2%
16/29 • Number of events 21 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Respiratory, thoracic and mediastinal disorders
Cold Systems
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17.2%
5/29 • Number of events 6 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Respiratory, thoracic and mediastinal disorders
Congestion
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13.8%
4/29 • Number of events 4 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Respiratory, thoracic and mediastinal disorders
Cough
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37.9%
11/29 • Number of events 12 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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General disorders
Other
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96.6%
28/29 • Number of events 168 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Metabolism and nutrition disorders
Decreased Feeding
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41.4%
12/29 • Number of events 13 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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General disorders
Dehydration
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3.4%
1/29 • Number of events 1 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Skin and subcutaneous tissue disorders
Diaper Rash
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31.0%
9/29 • Number of events 11 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Renal and urinary disorders
Diarrhea
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41.4%
12/29 • Number of events 17 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Respiratory, thoracic and mediastinal disorders
Difficulty Breathing
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13.8%
4/29 • Number of events 6 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Skin and subcutaneous tissue disorders
Eczema
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13.8%
4/29 • Number of events 4 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Skin and subcutaneous tissue disorders
Edema
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3.4%
1/29 • Number of events 1 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Hepatobiliary disorders
Elevated Bilirubin
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24.1%
7/29 • Number of events 10 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Hepatobiliary disorders
Elevated INR
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20.7%
6/29 • Number of events 7 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Hepatobiliary disorders
Elevation in AST and/or ALT
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6.9%
2/29 • Number of events 2 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Cardiac disorders
Elevation in Systolic BP > 112
|
24.1%
7/29 • Number of events 9 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Gastrointestinal disorders
Emesis
|
37.9%
11/29 • Number of events 21 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Metabolism and nutrition disorders
Feeding Intolerance
|
3.4%
1/29 • Number of events 1 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Infections and infestations
Fever
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62.1%
18/29 • Number of events 51 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Psychiatric disorders
Fussiness
|
10.3%
3/29 • Number of events 7 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
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Gastrointestinal disorders
Gastrointestinal
|
10.3%
3/29 • Number of events 3 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Hepatobiliary disorders
Hepatic
|
44.8%
13/29 • Number of events 24 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Cardiac disorders
Hypotension
|
3.4%
1/29 • Number of events 1 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
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Immune system disorders
Immunological
|
10.3%
3/29 • Number of events 3 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Metabolism and nutrition disorders
Inadequate wait gain
|
6.9%
2/29 • Number of events 2 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Hepatobiliary disorders
Increased PT/INR
|
6.9%
2/29 • Number of events 3 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
General disorders
Increased Sleepiness
|
24.1%
7/29 • Number of events 8 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Infections and infestations
Infectious
|
72.4%
21/29 • Number of events 63 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
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Psychiatric disorders
Irritability
|
34.5%
10/29 • Number of events 19 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Renal and urinary disorders
Jaundice
|
31.0%
9/29 • Number of events 15 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Metabolism and nutrition disorders
Metabolic
|
3.4%
1/29 • Number of events 1 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
6.9%
2/29 • Number of events 2 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplastic
|
3.4%
1/29 • Number of events 2 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Metabolism and nutrition disorders
Nutritional
|
34.5%
10/29 • Number of events 13 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
General disorders
Oral Thrush
|
10.3%
3/29 • Number of events 4 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Infections and infestations
Otitis Media
|
10.3%
3/29 • Number of events 5 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Metabolism and nutrition disorders
Poor Weight Gain
|
37.9%
11/29 • Number of events 11 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Surgical and medical procedures
Post Operative Liver Transplant
|
41.4%
12/29 • Number of events 12 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Skin and subcutaneous tissue disorders
Pruitis
|
20.7%
6/29 • Number of events 7 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Respiratory, thoracic and mediastinal disorders
RSV
|
6.9%
2/29 • Number of events 2 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
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Skin and subcutaneous tissue disorders
Rash
|
17.2%
5/29 • Number of events 8 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Gastrointestinal disorders
Reflux
|
13.8%
4/29 • Number of events 5 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Surgical and medical procedures
Surgical
|
6.9%
2/29 • Number of events 2 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Infection
|
17.2%
5/29 • Number of events 8 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
|
|
Gastrointestinal disorders
Vomitting
|
48.3%
14/29 • Number of events 20 • Adverse event data was collected from enrollment into the study until the earlier of the Day 365 visit or withdrawal from the study.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place