Clinical trial NCT06699849: Safety, Efficacy, and Pharmacokinetics of CSL889 in Adults and Adolescents With Sickle Cell Disease During Vaso-Occlusive Crisis
Official title: A Phase 2/Phase 3, Multicenter, Randomized, Multiple-Dose, Double-Blind, Placebo-Controlled Adaptive Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of CSL889 in Adults and Adolescents With Sickle Cell Disease During Vaso-Occlusive Crisis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Sickle Cell Disease Vaso-occlusive Crisis
Keywords: Sickle cell disease
Acute kidney injury
Pharmacokinetics
Acute chest syndrome
Vaso-occlusive crisis
Hemopexin
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2024-11-21
Enrollment: 260
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 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.

Primary outcomes:
measure: Time to resolution of VOC (time to discontinuation of parenteral opioids)
timeFrame: Up to Day 28 (End of study [EOS] Visit)
measure: Number of participants with treatment-emergent adverse events (TEAEs)
timeFrame: Up to Day 28 after CSL889 infusion (EOS Visit)
measure: Percentage of participants with TEAEs
timeFrame: Up to Day 28 after CSL889 infusion (EOS Visit)
measure: Number of participants with detectable treatment emergent (TE) anti-CSL889 antibodies
timeFrame: Up to Day 28 after CSL889 infusion (EOS Visit)
measure: Percentage of participants with detectable TE anti-CSL889 antibodies
timeFrame: Up to Day 28 after CSL889 infusion (EOS Visit)
Secondary outcomes:
measure: Hospital admission rate
timeFrame: Up to Day 28 after CSL889 infusion (EOS Visit)
measure: Length of hospital stay (If hospitalized)
timeFrame: Up to Day 28 (EOS Visit)
measure: Percentage of participants experiencing acute chest syndrome (ACS), acute kidney injury (AKI), or stroke
timeFrame: From the start of investigational product (IP) administration up to Day 8
measure: Length of acute care stay
timeFrame: Up to Day 28 (EOS Visit)
measure: Total Length of acute care and hospital stay
timeFrame: Up to Day 28 (EOS Visit)
measure: Re-presentation rate to an acute care facility for VOC or ACS after discharge
timeFrame: During the 30 days after discharge or at Day 90, whichever comes first
measure: Hospital admission rate for VOC or ACS after discharge
timeFrame: During the 30 days after discharge or at Day 90, whichever comes first
measure: Opioid consumption
timeFrame: From the time of enrollment to discharge (up to Day 28 [EOS Visit])
measure: Percentage of participants with >=30% pain reduction by NRS score
timeFrame: Within 4 hours after the start of CSL889 infusion
measure: Maximum observed concentration (Cmax) after Doses 1 and 3 of CSL889
timeFrame: Before dosing, and up to 12 hours after Doses 1 and 3
measure: Area under the concentration (AUCtau) after Doses 1 and 3 of CSL889
timeFrame: Before dosing, and up to 12 hours after Doses 1 and 3
measure: Time of maximum concentration (Tmax) after Doses 1 and 3 of CSL889
timeFrame: Before dosing, and up to 12 hours after Doses 1 and 3
measure: Trough concentration (Ctrough) after each dose of CSL889
timeFrame: Up to Day 5
measure: Accumulation ratio (AR) for AUCtau of CSL889 (the ratio between the AUCtau of Doses 3 and 1)
timeFrame: Before dosing and at up to 12 hours after Doses 1 and 3
measure: AR for Cmax of CSL889 (the ratio between the Cmax of Doses 3 and 1)
timeFrame: Before dosing and at up to 12 hours after Doses 1 and 3
measure: AR for Ctrough of CSL889 (the ratio between the Ctrough of the last dose and Dose 1)
timeFrame: Before dosing and after Dose 1 and the last dose
measure: Ctrough after each dose in sparse PK subset of CSL889
timeFrame: Up to Day 5
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Hollywood
country: United States
facility: The Foundation for Sickle Cell Disease
state: Florida
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
Study officials:
affiliation: CSL Behring
name: Study Director
role: STUDY_DIRECTOR
References: