Stannsoporfin With Light Therapy for Newborn Babies With Jaundice (JASMINE_204)

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

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.

Study Overview

• Status: Completed
• Conditions: Hyperbilirubinemia, Neonatal; Jaundice, Neonatal
• Intervention / Treatment: Procedure: Phototherapy; Drug: Placebo; Drug: Stannsoporfin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Colton, California, United States, 92324
      • Arrowhead Regional Medical Center
    • San Diego, California, United States, 92103
      • University of California San Diego Medical Center
    • San Francisco, California, United States, 94145
      • University of CA, San Francisco
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Univ Florida Hospital
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Hospital
    • Louisville, Kentucky, United States, 40202
      • Kosair Children's Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Univ Med Ctr of Southern Nevada
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers University Hospital
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • Stony Brook, New York, United States, 22794
      • Stoney Brook Univ Hospital
  • North Carolina
    • Raleigh, North Carolina, United States, 27610
      • WakeMed Health and Hospitals
  • Ohio
    • Toledo, Ohio, United States, 43606
      • Toledo Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
      • Hahnemann University Hospital/St. Christopher's Hospital for Children
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical Univ Of South Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee Health Science Center
  • Texas
    • Fort Worth, Texas, United States, 76104
      • JPS Health Network
    • Galveston, Texas, United States, 77555
      • Univ Texas Medical Branch
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Children's Hospital of Richmond at VCU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 hour to 3 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. Parental or guardian consent
3. Birth weight ≥ 2500 grams
4. 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)
5. Parents agree to observe light precautions for 10 days post treatment

Exclusion Criteria:

1. Elevated direct bilirubin ≥2 mg/dL, OR > 20% of the total serum bilirubin
2. Alanine aminotransferase (ALT) > 2 times the upper limit of normal (ULN) and/or aspartate aminotransferase (AST) > 3 times ULN
3. Abnormal renal function defined as creatinine and/or blood urea nitrogen >2 times the ULN
4. 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
5. Apgar score ≤6 at age 5 minutes
6. An unexplained existing rash or skin erythema
7. Prior exposure to PT
8. Clinical suggestion of neonatal thyroid disease or current uncontrolled thyroid disease in the mother (maternal Hashimoto's disease is not exclusionary)
9. Cardio-respiratory distress, defined as a respiratory rate >60 breaths per minute at time of enrollment
10. Any abnormal auditory or ophthalmologic findings on screening physical exam
11. 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
12. Known porphyrias or risk factors for porphyrias, including family history
13. A maternal history of systemic lupus erythematosus
14. Maternal use of phenobarbital 30 days before, or after delivery, if breast-feeding
15. 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
16. Significant congenital anomalies or infections
17. Risk of requiring surgery or exposure to operating room (OR) lights in the first 2 weeks of life
18. Persistent hypoglycemia (blood glucose <40 mg/dL)
19. Temperature instability defined as temperature consistently (3 consecutive times) <36 degrees centigrade (ºC) and/or >37.5 degrees centigrade (ºC) axillary
20. Use of intravenous immunoglobulin (IVIg) or albumin prior to study drug administration
21. Post-delivery treatment with medications that are known or suspected to displace bilirubin from albumin (e.g., ceftriaxone or sulfa-based antibiotics)
22. Use of photosensitizing drugs or agents
23. Unwillingness of parents/guardians to adhere to recommendations regarding light precautions
24. Exposure to any investigational medications or devices after delivery, or participation in another clinical trial while participating in this trial
25. Any other concurrent medical condition, which in the opinion of the Investigator, makes the patient unsuitable for the clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: InfaCare Pharmaceuticals Corporation, a Mallinckrodt Company
• Investigators: Study Director: Global Clinical Leader, InfaCare Pharmaceuticals Corporation, a Mallinckrodt Company

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2013
• Primary Completion (Actual): March 22, 2016
• Study Completion (Actual): March 22, 2016

Study Registration Dates

• First Submitted: June 24, 2013
• First Submitted That Met QC Criteria: June 24, 2013
• First Posted (Estimate): June 26, 2013

Study Record Updates

• Last Update Posted (Actual): February 6, 2020
• Last Update Submitted That Met QC Criteria: February 4, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: G6PD deficiency; Antibody (ABO) incompatibility; Coombs positive ABO/ rhesus factor (RH) incompatibility; Intensive phototherapy in neonates
• Additional Relevant MeSH Terms: Pathologic Processes; Infant, Newborn, Diseases; Skin Manifestations; Jaundice; Hyperbilirubinemia; Hyperbilirubinemia, Neonatal; Jaundice, Neonatal; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Tin mesoporphyrin
• Other Study ID Numbers: 64,185-204