Hyperbilirubinemia, Neonatal
Conditions
Keywords
Hemolysis
Brief summary
It is a normal process in the human body for red blood cells to die, which makes bilirubin. Bilirubin is cleared away through the liver. Some babies are born with livers that don't work well enough yet, or their red blood cells are dying too fast, so the baby looks yellow (jaundice). This means there is too much bilirubin in the body. It can be dangerous if a baby's bilirubin gets too high. Phototherapy is what they call the lights they shine on newborn babies to help the liver get rid of bilirubin. This study tests an experimental drug to see if it can reduce how much bilirubin is being made in the first place.
Detailed description
The purpose of this study is to determine if an experimental drug, stannsoporfin, is safe and effective in the treatment of hyperbilirubinemia in hemolyzing neonates.
Interventions
DRUGStannsoporfin
Stannsoporfin administered as a single IM injection
OTHERPlacebo
Placebo (sterile saline solution) administered as a single IM injection
PT standard care administered as needed, based on bilirubin levels throughout the treatment period
Sponsors
InfaCare Pharmaceuticals Corporation, a Mallinckrodt Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Clinical personnel at the site (including investigator, study coordinator and central cardiologist) were blinded to treatment group. The research pharmacy and the health care provider responsible for giving the injection to patients knew what the treatment was (they were not blinded).
Intervention model description
Sequential experimental cohorts are run in parallel with placebo controls.
Eligibility
Sex/Gender
ALL
Age
1 Minutes to 48 Hours
Healthy volunteers
No
Inclusion criteria
Babies may only participate if they meet all the following criteria: * Is a term or late preterm baby * Is at risk for protocol-defined hemolytic disease * Weighs at least 2500 g (5.5 lbs) * Has total serum bilirubin (TSB) a specified amount lower than the phototherapy threshold for the age * Has parents/guardians who are willing to follow light precautions and sign informed consent
Exclusion criteria
The following criteria will make a baby not eligible to participate: * Needs medications that may prolong the QT interval * Has family history or risk factors for Long QT Syndrome, Sudden Infant Death Syndrome, or Porphyrias * Has an Apgar score of 6 or below at age 5 minutes * Has abnormalities or infections (in mother or child) that per protocol or in the opinion of the investigator may compromise the safety and well-being of the baby or analysis of study results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Adjusted Total Serum Bilirubin (TSB) From Baseline to 48 Hours After Treatment. | Baseline, 48 hours | The adjusted TSB is a calculation of the percentage difference of the TSB level from the age-specific threshold for PT initiation per the American Academy of Pediatrics (AAP) Guidelines, ie, an indication of the distance below the PT threshold at the time \[(TSB - PT threshold/PT threshold) x 100%). |
| Change From Baseline in Total Serum Bilirubin (TSB) at 48 Hours (ITT Population | Baseline, 48 hrs | Total bilirubin in blood serum was measured at baseline and at 48 hours after the shot. Change from baseline is calculated by subtracting the amount at baseline from the amount at 48 hours. Lower numbers are better. |
Countries
Poland, Spain, Ukraine, United States
Participant flow
Recruitment details
Fifty-eight (58) babies were enrolled before the trial was prematurely terminated due to cancellation.
Pre-assignment details
Because the cohorts were run sequentially, and the trial was cancelled before they were all enrolled, Cohort 3 enrolled only 8 compared to 15 in Cohort 4.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Stannsoporfin 1.5 mg/kg 1.5 mg/kg stannsoporfin (with phototherapy as needed) | 17 |
| Cohort 2: Stannsoporfin 3.0 mg/kg 3.0 mg/kg stannsoporfin (with phototherapy as needed) | 18 |
| Cohort 3: Stannsoporfin 4.5 mg/kg 4.5 mg/kg stannsoporfin (with phototherapy as needed) | 8 |
| Cohort 4: Placebo Control Placebo control was sterile saline solution (with phototherapy as needed) | 15 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Parent/Guardian Voluntarily Withdrew | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1: Stannsoporfin 1.5 mg/kg | Cohort 2: Stannsoporfin 3.0 mg/kg | Cohort 3: Stannsoporfin 4.5 mg/kg | Cohort 4: Placebo Control | Total |
|---|---|---|---|---|---|
| Age, Customized 35 through 37 Weeks | 2 Participants | 0 Participants | 1 Participants | 3 Participants | 6 Participants |
| Age, Customized 38 Weeks and Above | 15 Participants | 18 Participants | 7 Participants | 12 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 6 Participants | 6 Participants | 4 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 12 Participants | 2 Participants | 11 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 2 Participants | 0 Participants | 2 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 4 Participants | 3 Participants | 0 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants | 5 Participants | 11 Participants |
| Race (NIH/OMB) White | 7 Participants | 7 Participants | 6 Participants | 3 Participants | 23 Participants |
| Sex: Female, Male Female | 10 Participants | 6 Participants | 6 Participants | 7 Participants | 29 Participants |
| Sex: Female, Male Male | 7 Participants | 12 Participants | 2 Participants | 8 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 18 | 0 / 8 | 0 / 15 |
| other Total, other adverse events | 8 / 17 | 10 / 18 | 3 / 8 | 5 / 15 |
| serious Total, serious adverse events | 0 / 17 | 1 / 18 | 1 / 8 | 2 / 15 |
Outcome results
Primary
Change From Baseline in Total Serum Bilirubin (TSB) at 48 Hours (ITT Population
Total bilirubin in blood serum was measured at baseline and at 48 hours after the shot. Change from baseline is calculated by subtracting the amount at baseline from the amount at 48 hours. Lower numbers are better.
Time frame: Baseline, 48 hrs
Population: Intention-to-treat
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: Stannsoporfin 1.5 mg/kg | Change From Baseline in Total Serum Bilirubin (TSB) at 48 Hours (ITT Population | at Baseline | 7.80 mg/dL |
| Cohort 1: Stannsoporfin 1.5 mg/kg | Change From Baseline in Total Serum Bilirubin (TSB) at 48 Hours (ITT Population | Change from Baseline at 48 hours | 2.70 mg/dL |
| Cohort 1: Stannsoporfin 1.5 mg/kg | Change From Baseline in Total Serum Bilirubin (TSB) at 48 Hours (ITT Population | at 48 hours | 10.90 mg/dL |
| Cohort 2: Stannsoporfin 3.0 mg/kg | Change From Baseline in Total Serum Bilirubin (TSB) at 48 Hours (ITT Population | at Baseline | 8.45 mg/dL |
| Cohort 2: Stannsoporfin 3.0 mg/kg | Change From Baseline in Total Serum Bilirubin (TSB) at 48 Hours (ITT Population | Change from Baseline at 48 hours | 2.94 mg/dL |
| Cohort 2: Stannsoporfin 3.0 mg/kg | Change From Baseline in Total Serum Bilirubin (TSB) at 48 Hours (ITT Population | at 48 hours | 11.65 mg/dL |
| Cohort 3: Stannsoporfin 4.5 mg/kg | Change From Baseline in Total Serum Bilirubin (TSB) at 48 Hours (ITT Population | at 48 hours | 10.35 mg/dL |
| Cohort 3: Stannsoporfin 4.5 mg/kg | Change From Baseline in Total Serum Bilirubin (TSB) at 48 Hours (ITT Population | at Baseline | 9.35 mg/dL |
| Cohort 3: Stannsoporfin 4.5 mg/kg | Change From Baseline in Total Serum Bilirubin (TSB) at 48 Hours (ITT Population | Change from Baseline at 48 hours | 1.45 mg/dL |
| Placebo Control | Change From Baseline in Total Serum Bilirubin (TSB) at 48 Hours (ITT Population | at Baseline | 8.00 mg/dL |
| Placebo Control | Change From Baseline in Total Serum Bilirubin (TSB) at 48 Hours (ITT Population | Change from Baseline at 48 hours | 3.70 mg/dL |
| Placebo Control | Change From Baseline in Total Serum Bilirubin (TSB) at 48 Hours (ITT Population | at 48 hours | 11.90 mg/dL |
Comparison: Last Observation Carry Forward (LOCF) is used to impute missing post-baseline TSB. Analysis of covariance (ANCOVA) is conducted for TSB including treatment and gestational age as fixed effects and baseline TSB as a covariate. Least-squares means (LS means) and standard errors (SEM) are estimated for each treatment group and placebo. LS mean difference, 95% Confidence Interval, and p-value are estimated based on LS mean difference between each stannsoporfin group and placebo.p-value: =0.06195% CI: [-3.71, 0.09]ANCOVA
Comparison: Last Observation Carry Forward (LOCF) is used to impute missing post-baseline TSB. Analysis of covariance (ANCOVA) is conducted for TSB including treatment and gestational age as fixed effects and baseline TSB as a covariate. Least-squares means (LS means) and standard errors (SEM) are estimated for each treatment group and placebo. LS mean difference, 95% Confidence Interval, and p-value are estimated based on LS mean difference between each stannsoporfin group and placebo.p-value: =0.16395% CI: [-3.24, 0.56]ANCOVA
Comparison: Last Observation Carry Forward (LOCF) is used to impute missing post-baseline TSB. Analysis of covariance (ANCOVA) is conducted for TSB including treatment and gestational age as fixed effects and baseline TSB as a covariate. Least-squares means (LS means) and standard errors (SEM) are estimated for each treatment group and placebo. LS mean difference, 95% Confidence Interval, and p-value are estimated based on LS mean difference between each stannsoporfin group and placebo.p-value: =0.02895% CI: [-4.97, -0.3]ANCOVA
Primary
Change in Adjusted Total Serum Bilirubin (TSB) From Baseline to 48 Hours After Treatment.
The adjusted TSB is a calculation of the percentage difference of the TSB level from the age-specific threshold for PT initiation per the American Academy of Pediatrics (AAP) Guidelines, ie, an indication of the distance below the PT threshold at the time \[(TSB - PT threshold/PT threshold) x 100%).
Time frame: Baseline, 48 hours
Population: Intent-to-treat population (ITT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Stannsoporfin 1.5 mg/kg | Change in Adjusted Total Serum Bilirubin (TSB) From Baseline to 48 Hours After Treatment. | -12.30 percentage difference from PT threshold |
| Cohort 2: Stannsoporfin 3.0 mg/kg | Change in Adjusted Total Serum Bilirubin (TSB) From Baseline to 48 Hours After Treatment. | -9.05 percentage difference from PT threshold |
| Cohort 3: Stannsoporfin 4.5 mg/kg | Change in Adjusted Total Serum Bilirubin (TSB) From Baseline to 48 Hours After Treatment. | -19.95 percentage difference from PT threshold |
| Placebo Control | Change in Adjusted Total Serum Bilirubin (TSB) From Baseline to 48 Hours After Treatment. | -5.7 percentage difference from PT threshold |
Comparison: Last Observation Carry Forward (LOCF) is used to impute missing post-baseline TSB. Least-squares means are from an ANCOVA model for adjusted TSB with treatment and gestational age as fixed effects and baseline adjusted TSB as a covariate. TSB is calculated as \[(TSB - Phototherapy(PT) threshold)/ PT threshold \] X 100%.p-value: =0.0495% CI: [-26.27, -0.62]ANCOVA
p-value: =0.11795% CI: [-22.61, 2.58]ANCOVA
p-value: =0.05795% CI: [-30.31, 0.44]ANCOVA