This is a phase 2, randomized, multiple-dose, placebo-controlled study designed to evaluate the safety, efficacy, and pharmacokinetics (PK) of CSL889 (human hemopexin) when given intravenously (IV) to adults and adolescents with sickle cell disease (SCD) experiencing vaso-occlusive crises (VOC). The main objectives of the study are to evaluate the safety and tolerability of CSL889 in study participants, and to assess how CSL889 affects the time it takes for VOC to resolve in participants with SCD.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
70
CSL889 is a solution for infusion to be administered by the IV route.
Volume and regimen matched to CSL889 will be administered.
University of California Irvine
Orange, California, United States
Golisano Children's Hospital
Fort Myers, Florida, United States
The Foundation for Sickle Cell Disease
Hollywood, Florida, United States
University of Maryland
Baltimore, Maryland, United States
Henry Ford Health System
Detroit, Michigan, United States
Mount Sinai Medical Center
New York, New York, United States
Jacobi Medical Center
The Bronx, New York, United States
University of Cincinnati
Cincinnati, Ohio, United States
The Ohio State University
Columbus, Ohio, United States
Hacettepe Universitesi
Ankara, Turkey (Türkiye)
...and 2 more locations
Number of participants with treatment-emergent adverse events (TEAEs)
Time frame: Up to Day 28 (End of study [EOS] Visit)
Percentage of participants with TEAEs
Time frame: Up to Day 28 (EOS Visit)
Number of participants with detectable treatment emergent (TE) anti-CSL889 antibodies
Time frame: Up to Day 28 (EOS Visit)
Percentage of participants with detectable TE anti-CSL889 antibodies
Time frame: Up to Day 28 (EOS Visit)
Time to resolution of VOC (time to discontinuation of parenteral opioids)
Time frame: Up to Day 28 (EOS Visit)
Hospital admission rate
Hospital admission rate in participants with SCD presenting with VOC who received greater than or equal to (≥) 1 dose of CSL889 in the acute care setting.
Time frame: Up to Day 28 (EOS Visit)
Length of hospital stay (If hospitalized)
Time frame: Up to Day 28 (EOS Visit)
Percentage of participants experiencing acute chest syndrome (ACS), acute kidney injury (AKI), or stroke
Time frame: From the start of investigational product (IP) administration up to Day 8
Length of acute care stay
Time frame: Up to Day 28 (EOS Visit)
Total Length of acute care and hospital stay
Time frame: Up to Day 28 (EOS Visit)
Re-presentation rate to an acute care facility for VOC or ACS after discharge
Time frame: From discharge up to Day 28
Hospital admission rate for VOC or ACS after discharge
Time frame: From discharge up to Day 28
Opioid consumption
Opioid consumption will be measured in morphine milligram equivalent units.
Time frame: From the time of enrollment to discharge (up to Day 28 [EOS Visit])
Number of participants with ≥ 30% pain reduction by Numeric Rating Scale (NRS) score
The NRS for pain is a validated self-reported 11-point pain severity scale (where 0 means no pain and 10 means the most or worst possible pain) that can be used in adults, adolescents, and children ≥ 8 years of age with SCD.
Time frame: Within 4 hours after the start of CSL889 infusion
Percentage of participants with ≥ 30% pain reduction by NRS score
The NRS for pain is a validated self-reported 11-point pain severity scale (where 0 means no pain and 10 means the most or worst possible pain) that can be used in adults, adolescents, and children ≥ 8 years of age with SCD.
Time frame: Within 4 hours after the start of CSL889 infusion
Maximum observed concentration (Cmax) after Doses 1 and 3 of CSL889
Time frame: Before dosing, and up to 12 hours after Doses 1 and 3
Area under the concentration (AUCtau) after Doses 1 and 3 of CSL889
Time frame: Before dosing, and up to 12 hours after Doses 1 and 3
Time of maximum concentration (Tmax) after Doses 1 and 3 of CSL889
Time frame: Before dosing, and up to 12 hours after Doses 1 and 3
Trough concentration (Ctrough) after each dose of CSL889
Time frame: Up to Day 5
Accumulation ratio (AR) for AUCtau of CSL889 (the ratio between the AUCtau of Doses 3 and 1)
Time frame: Before dosing and at up to 12 hours after Doses 1 and 3
AR for Cmax of CSL889 (the ratio between the Cmax of Doses 3 and 1)
Time frame: Before dosing and at up to 12 hours after Doses 1 and 3
AR for Ctrough of CSL889 (the ratio between the Ctrough of the last dose and Dose 1)
Time frame: Before dosing and after Dose 1 and the last dose
Cmax after each dose in Sparse PK subset of CSL889
Sparse PK blood sampling will be performed in remainder of participants who are not in the Adult or Adolescent PK Subsets.
Time frame: Up to Day 5
Ctrough after each dose in Sparse PK subset of CSL889
Sparse PK blood sampling will be performed in remainder of participants who are not in the Adult or Adolescent PK Subsets.
Time frame: Up to Day 5
AR for Cmax in Sparse PK subset of CSL889
Sparse PK blood sampling will be performed in remainder of participants who are not in the Adult or Adolescent PK Subsets.
Time frame: Up to Day 5
AR for Ctrough in Sparse PK subset of CSL889
Sparse PK blood sampling will be performed in remainder of participants who are not in the Adult or Adolescent PK Subsets.
Time frame: Up to Day 5
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