Stannsoporfin With Light Therapy for Newborn Babies With Jaundice

Study Overview
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Brief Summary
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It is normal for red blood cells to die, even in newborn babies. The waste from that is called bilirubin. The liver clears bilirubin out of the body. Some babies are born with illness that makes red blood cells die too fast, so the liver is not strong enough to keep up with it. The yellowish color in eyes or skin means there is too much bilirubin in the body. It can be dangerous if a baby's bilirubin gets too high. Special lights are put on jaundiced babies (called phototherapy) to help the liver get rid of bilirubin. This study tests an experimental drug to see if it can help the liver even more, by safely cutting down the amount of bilirubin the body is making in the first place.

Detailed Description
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Participants randomized (1:1:1) to treatment groups will be term or near-term infants with isoimmune hemolytic disease or glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Official Title
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A Phase 2b Multicenter, Single Dose, Randomized, Double Blind, Placebo-Controlled, Parallel-Group Study Evaluating the Safety and Efficacy of Two Doses of Stannsoporfin in Combination With Phototherapy in Neonates

Conditions
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Jaundice, Neonatal, Hyperbilirubinemia, Neonatal

Intervention / Treatment
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* Procedure: Phototherapy
* Drug: Stannsoporfin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Term and near term infants ≥35 and ≤ 43 weeks gestational age (GA), age 0-48 hours with antibody (ABO) or rhesus factor (Rh) incompatibility (anti C, c, D, E or e) who are Coombs positive, or age 0-72 hours with G6PD deficiency Parental or guardian consent Birth weight ≥ 2500 grams At or above the age-specific threshold for initiating phototherapy (PT) per the American Academy of Pediatrics (AAP) guidelines based on measurement of total serum bilirubin (TSB) Parents agree to observe light precautions for 10 days post treatment Exclusion Criteria: Elevated direct bilirubin ≥2 mg/dL, OR > 20% of the total serum bilirubin Alanine aminotransferase (ALT) > 2 times the upper limit of normal (ULN) and/or aspartate aminotransferase (AST) > 3 times ULN Abnormal renal function defined as creatinine and/or blood urea nitrogen >2 times the ULN Any other clinically significant abnormalities on screening laboratory evaluation [including electrocardiogram (ECG)] that in the opinion of the investigator makes the patient unsuitable for the clinical trial Apgar score ≤6 at age 5 minutes An unexplained existing rash or skin erythema Prior exposure to PT Clinical suggestion of neonatal thyroid disease or current uncontrolled thyroid disease in the mother (maternal Hashimoto's disease is not exclusionary) Cardio-respiratory distress, defined as a respiratory rate >60 breaths per minute at time of enrollment Any abnormal auditory or ophthalmologic findings on screening physical exam Treatment or need for treatment in the neonate with medications that are photoreactive or may prolong the QT interval (erythromycin ointment for eye prophylaxis is permitted), or family history of Long QT syndrome Known porphyrias or risk factors for porphyrias, including family history A maternal history of systemic lupus erythematosus Maternal use of phenobarbital 30 days before, or after delivery, if breast-feeding Maternal current drug or alcohol abuse, or maternal history of drug or alcohol abuse that, in the opinion of the Investigator, would not make the patient a suitable candidate for participation in the clinical trial Significant congenital anomalies or infections Risk of requiring surgery or exposure to operating room (OR) lights in the first 2 weeks of life Persistent hypoglycemia (blood glucose <40 mg/dL) Temperature instability defined as temperature consistently (3 consecutive times) <36 degrees centigrade (ºC) and/or >37.5 degrees centigrade (ºC) axillary Use of intravenous immunoglobulin (IVIg) or albumin prior to study drug administration Post-delivery treatment with medications that are known or suspected to displace bilirubin from albumin (e.g., ceftriaxone or sulfa-based antibiotics) Use of photosensitizing drugs or agents Unwillingness of parents/guardians to adhere to recommendations regarding light precautions Exposure to any investigational medications or devices after delivery, or participation in another clinical trial while participating in this trial Any other concurrent medical condition, which in the opinion of the Investigator, makes the patient unsuitable for the clinical trial

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 72 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants receive placebo and phototherapy | Procedure: Phototherapy<br>* Phototherapy starts within 30 minutes before or after injection<br>* Other names: Light therapy;Drug: Placebo<br>* Matching placebo administered by IM injection<br>* Other names: Saline;|
| Experimental: Stannsoporfin 3.0 mg/kg<br>Participants receive stannsoporfin (3.0 mg/kg) and phototherapy | Procedure: Phototherapy<br>* Phototherapy starts within 30 minutes before or after injection<br>* Other names: Light therapy;Drug: Stannsoporfin<br>* Stannsoporfin (3.0 or 4.5 mg/kg) administered by intramuscular (IM) injection (a shot in the muscle)<br>* Other names: Experimental drug;|
| Experimental: Stannsoporfin 4.5 mg/kg<br>Participants receive stannsoporfin (4.5 mg/kg) and phototherapy | Procedure: Phototherapy<br>* Phototherapy starts within 30 minutes before or after injection<br>* Other names: Light therapy;Drug: Stannsoporfin<br>* Stannsoporfin (3.0 or 4.5 mg/kg) administered by intramuscular (IM) injection (a shot in the muscle)<br>* Other names: Experimental drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Serum Bilirubin (mg/dL) | Total serum bilirubin (TSB) was measured at baseline (the measure that qualified the baby for inclusion) and at 48 hours after treatment. If a baby was discharged before 48 hours, the last measurement before discharge was used [last observation carried forward (LOCF)]. | Baseline, 48 hours post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time (Hour) at Which TSB First Crosses at or Below the Defined Age-specific Threshold for 54-hours Post-treatment (PT) | The hour that 50% of babies in the group (median) first crosses at or below the defined 54-hour threshold for the baby's age | within 54 hours | 
| Number of Participants With Phototherapy (PT) Failure | PT failure was defined by any of the following: re-start of PT within 6 hours after stopping re-hospitalization for hyperbilirubinaemia use of intravenous immunoglobulin (IVIg) need for an exchange transfusion | within 30 days after discharge | 
| Number of Participants With Rebound Hyperbilirubinemia | Rebound hyperbilirubinaemia was defined as an increase in TSB above the age-specific threshold for initiating phototherapy, following the discontinuation of the initial phototherapy. | within 54 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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G6PD deficiency, Antibody (ABO) incompatibility, Coombs positive ABO/ rhesus factor (RH) incompatibility, Intensive phototherapy in neonates