Safety, Efficacy, and Pharmacokinetics of CSL889 in Adults and Adolescents With Sickle Cell Disease During Vaso-Occlusive Crisis

A Phase 2, Multicenter, Randomized, Multiple-Dose, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of CSL889 in Adults and Adolescents With Sickle Cell Disease During Vaso-Occlusive Crisis

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 Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease Vaso-occlusive Crisis
• Intervention / Treatment: Biological: CSL889; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Trial Registration Coordinator; Phone Number: +1 610-878-4697; Email: clinicaltrials@cslbehring.com

Study Locations

• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01120
    • Recruiting
    • Baskent University School of Medicine
  • Ankara, Turkey (Türkiye), 06230
    • Not yet recruiting
    • Hacettepe Universitesi
    • Contact: Central Contact
  • Istanbul, Turkey (Türkiye), 34093
    • Not yet recruiting
    • Istanbul Universitesi
    • Contact: Central Contact
  • Mezitli-Mersin, Turkey (Türkiye), 33200
    • Recruiting
    • Medical Park Mersin Hospital
  • Seyhan, Turkey (Türkiye), 01130
    • Not yet recruiting
    • Özel Acibadem Adana Hastanesi
    • Contact: Central Contact
  • Seyhan/Adana, Turkey (Türkiye), 01130
    • Recruiting
    • Özel Acibadem Adana Hastanesi
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guy's Hospital
• United States
  • California
    • Oakland, California, United States, 94609
      • Recruiting
      • Univ. of California, San Francisco Health Care
    • Orange, California, United States, 92868
      • Not yet recruiting
      • University of California Irvine
      • Contact: Use Central Contact
  • Florida
    • Fort Myers, Florida, United States, 33908
      • Recruiting
      • Golisano Children's Hospital
      • Contact: Use Central Contact
    • Hollywood, Florida, United States, 33023-6703
      • Recruiting
      • The Foundation for Sickle Cell Disease
      • Contact: Use Central Contact
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Recruiting
      • Arthur M. Blank Hospital-Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois at Chicago
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • University of Louisville Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland
      • Contact: Use Central Contact
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Health System
      • Contact: Use Central Contact
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Detroit Medical Center
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • St. Louis Children's Hospital
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai Medical Center
      • Contact: Use Central Contact
    • The Bronx, New York, United States, 10461
      • Recruiting
      • Jacobi Medical Center
      • Contact: Central Contact
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Recruiting
      • East Carolina University
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati
      • Contact: Use Central Contact
    • Columbus, Ohio, United States, 43085
      • Recruiting
      • The Ohio State University
      • Contact: Use Central Contact
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • Hillman Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • University of Pittsburgh
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• At the time of informed consent:

  • 18 years of age (adults); or
  • 12 to less than (<) 18 years of age (adolescents, where approved and when enrollment for adolescents has been opened by the sponsor, with the endorsement of the Independent Data Monitoring Committee [IDMC])
• Diagnosed with SCD (any genotype).
• Presented at the study site with a new acute VOC necessitating treatment with parenteral opioids.

Exclusion Criteria:

• VOC pain onset greater than (>) 72 hours before administration of first parenteral opioid.
• Must not have a history of > 5 VOCs requiring hospital admission in the past 6 months; or signs and / or symptoms of ACS; or new neurological symptoms suggestive of acute stroke or transient ischemic attack; or any stage (acute kidney injury) AKI; or been discharged from inpatient hospital admission for VOC or other vaso-occlusive event within 14 days before the current presentation.
• Serum hemoglobin < 6 g/dL, serum ferritin ≥ 2000 ng/mL, receiving an approved medication for SCD that has not been on a stable, well-tolerated regimen, currently taking methadone or buprenorphine.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CSL889 Regimen 1; Participants in this arm will receive CSL889 as per regimen 1.	Biological: CSL889; CSL889 is a solution for infusion to be administered by the IV route.; Other Names: Hemopexin, human
Experimental: CSL889 Regimen 2; Participants in this arm will receive CSL889 as per regimen 2.	Biological: CSL889; CSL889 is a solution for infusion to be administered by the IV route.; Other Names: Hemopexin, human
Placebo Comparator: Placebo; Participants in this arm will receive placebo matching to CSL889 regimen.	Drug: Placebo; Volume and regimen matched to CSL889 will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment-emergent adverse events (TEAEs)	Up to Day 28 (End of study [EOS] Visit)
Percentage of participants with TEAEs	Up to Day 28 (EOS Visit)
Number of participants with detectable treatment emergent (TE) anti-CSL889 antibodies	Up to Day 28 (EOS Visit)
Percentage of participants with detectable TE anti-CSL889 antibodies	Up to Day 28 (EOS Visit)
Time to resolution of VOC (time to discontinuation of parenteral opioids)	Up to Day 28 (EOS Visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay (If hospitalized)		Up to Day 28 (EOS Visit)
Percentage of participants experiencing acute chest syndrome (ACS), acute kidney injury (AKI), or stroke		From the start of investigational product (IP) administration up to Day 8
Length of acute care stay		Up to Day 28 (EOS Visit)
Total Length of acute care and hospital stay		Up to Day 28 (EOS Visit)
Opioid consumption	Opioid consumption will be measured in morphine milligram equivalent units.	From the time of enrollment to discharge (up to Day 28 [EOS Visit])
Maximum observed concentration (Cmax) after Doses 1 and 3 of CSL889		Before dosing, and up to 12 hours after Doses 1 and 3
Area under the concentration (AUCtau) after Doses 1 and 3 of CSL889		Before dosing, and up to 12 hours after Doses 1 and 3
Time of maximum concentration (Tmax) after Doses 1 and 3 of CSL889		Before dosing, and up to 12 hours after Doses 1 and 3
Trough concentration (Ctrough) after each dose of CSL889		Up to Day 5
Accumulation ratio (AR) for AUCtau of CSL889 (the ratio between the AUCtau of Doses 3 and 1)		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)		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)		Before dosing and after Dose 1 and the last dose
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.	Up to Day 28 (EOS Visit)
Re-presentation rate to an acute care facility for VOC or ACS after discharge		From discharge up to Day 28
Hospital admission rate for VOC or ACS after discharge		From discharge up to Day 28
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.	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.	Within 4 hours after the start of CSL889 infusion
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.	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.	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.	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.	Up to Day 5

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2025
• Primary Completion (Estimated): October 22, 2027
• Study Completion (Estimated): October 22, 2027

Study Registration Dates

• First Submitted: November 19, 2024
• First Submitted That Met QC Criteria: November 19, 2024
• First Posted (Actual): November 21, 2024

Study Record Updates

• Last Update Posted (Actual): August 14, 2026
• Last Update Submitted That Met QC Criteria: August 13, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Acute kidney injury; Sickle cell disease; Vaso-occlusive crisis; Acute chest syndrome; Hemopexin
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Hematologic Diseases; Renal Insufficiency; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Acute Kidney Injury; Anemia, Sickle Cell; Acute Chest Syndrome; Vaso-Occlusive Crises; Amino Acids, Peptides, and Proteins; Proteins; Carbohydrates; Blood Proteins; Serum Globulins; Globulins; Glycoproteins; Glycoconjugates; Acute-Phase Proteins; Beta-Globulins; Hemopexin
• Other Study ID Numbers: CSL889_2001; 2024-513440-29-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
• IPD Sharing Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (i.e. FDA, EMA) is complete and the primary publication is available

IPD Sharing Access Criteria

Proposed research should seek to answer a previously unanswered important medical or scientific question.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No