Safety, Efficacy, and Pharmacokinetics of CSL889 in Adults and Adolescents With Sickle Cell Disease During Vaso-Occlusive Crisis
- Conditions
- Sickle Cell Disease Vaso-occlusive Crisis
- Interventions
- Biological: CSL889Drug: Placebo
- Registration Number
- NCT06699849
- Lead Sponsor
- CSL Behring
- Brief Summary
This study consists of two parts: phase 2 (Part A) and phase 3 (Part B). It is a multicenter study designed to evaluate the safety, effectiveness, 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 assess how CSL889 affects the time it takes for VOC to resolve in participants with SCD, and to evaluate the safety and tolerability of CSL889 in study participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 260
•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.
- VOC pain onset greater than or equal to (>=) 72 hours before administration of first parenteral opioid (Part A; may be adjusted for Part B based on prespecified analysis).
- Must not have a history of greater than (>) 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: CSL889 Regimen A1 CSL889 Participants in this arm will receive CSL889 as per regimen A1. Part A: CSL889 Regimen A2 CSL889 Participants in this arm will receive CSL889 as per regimen A2. Part A: CSL889 Regimen A3 CSL889 Participants in this arm will receive CSL889 as per regimen A3. Part A: Placebo Placebo Participants in this arm will receive placebo matching to CSL889 regimen of Part A. Part B: CSL889 CSL889 Participants in this arm will receive CSL889, as per regimen selected after Part A. Part B: Placebo Placebo Participants in this arm will receive placebo matching the selected CSL889 regimen after Part A.
- Primary Outcome Measures
Name Time Method Time to resolution of VOC (time to discontinuation of parenteral opioids) Up to Day 28 (End of study [EOS] Visit) Number of participants with treatment-emergent adverse events (TEAEs) Up to Day 28 after CSL889 infusion (EOS Visit) Percentage of participants with TEAEs Up to Day 28 after CSL889 infusion (EOS Visit) Number of participants with detectable treatment emergent (TE) anti-CSL889 antibodies Up to Day 28 after CSL889 infusion (EOS Visit) Percentage of participants with detectable TE anti-CSL889 antibodies Up to Day 28 after CSL889 infusion (EOS Visit)
- Secondary Outcome Measures
Name Time Method Hospital admission rate Up to Day 28 after CSL889 infusion (EOS Visit) 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.
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) Re-presentation rate to an acute care facility for VOC or ACS after discharge During the 30 days after discharge or at Day 90, whichever comes first Hospital admission rate for VOC or ACS after discharge During the 30 days after discharge or at Day 90, whichever comes first Opioid consumption From the time of enrollment to discharge (up to Day 28 [EOS Visit]) Opioid consumption will be measured in morphine milligram equivalent units.
Percentage of participants with >=30% pain reduction by NRS score Within 4 hours after the start of CSL889 infusion The Numeric Rating Scale (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.
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 Ctrough after each dose in sparse PK subset of CSL889 Up to Day 5 Sparse PK blood sampling will be performed in Part A participants who are not in the Adult or Adolescent PK Subsets.