A 2-Part, Phase 1, Multi-Center, Single-Dose, Open Label, Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CSL889 in Adult Patients With Sickle Cell Disease

CSL Behring15 sites in 3 countries28 target enrollmentMay 20, 2021

ConditionsSickle Cell Disease

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Sickle Cell Disease
Sponsor: CSL Behring
Enrollment: 28
Locations: 15
Primary Endpoint: Percentage of subjects with TEAEs by severity by Cohort
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is a phase 1, first-in-human, multi-center, open-label, single dose cohort study to evaluate the safety and tolerability, pharmacokinetics (PK), exploratory pharmacodynamics (PD), and biomarkers of target engagement of CSL889 following single intravenous (IV) doses in subjects with sickle cell disease (SCD). The study involves sequential dose escalation of cohorts with between-group assessments of key safety and PK variables.

Registry

clinicaltrials.gov

Start Date

May 20, 2021

End Date

July 24, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

CSL Behring

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Diagnosis of SCD as documented in the subject's medical record
•Aged 18 to 60 years, inclusive
•Stable SCD for at least 30 days before Day
•Stable SCD is defined as the subject being at his or her medical baseline, with no evidence of worsening of disease over the last 30 days (including VOC, recent major surgery, hospitalization, serious infection, significant bleeding, cerebrovascular accident, seizures, or IV opioids)(Part A)
•Uncomplicated VOC requiring parenteral opioid treatment and admission to hospital for management. Uncomplicated VOC is defined as sickle cell pain without the following associated clinical features (Part B):
•Fever (\> 38.5 °C)
•Hypotension (\< 90/60 mmHg)
•Hypoxia (\< 90% oxygen saturation on room air, or requiring oxygen therapy to maintain oxygen saturation above 90%)
•New neurological signs and / or symptoms clinically suggestive of stroke or transient ischemic attack
•Signs and / or symptoms of Acute Chest Syndrome, accompanied by any new pulmonary infiltrate on chest radiography (chest X-ray to be performed if clinically indicated and according to local clinical guidelines)

Exclusion Criteria

•History of primary hemorrhagic stroke
•History or evidence of inherited bleeding diathesis or significant coagulopathy at risk for bleeding
•Weight \>110 kg (242 lbs)
•Surgery within 30 days before Day 1 or any preplanned surgeries during the study (minor surgeries may be permitted under local anesthesia before screening, with permission of the medical monitor)
•Female subjects who are pregnant or breastfeeding
•Female subject of childbearing potential or fertile male subject either not using or not willing to use an acceptable method of contraception to avoid pregnancy during the study and for 30 days after receipt of CSL
•Treatment with any other drug / biologic that is newly approved for SCD during the conduct of this study within 90 days before Day
•Exceptions: crizanlizumab \[Adakveo®\] and voxelotor \[Oxbryta®\] \] are permitted (where prescribed).
•Treatment with another investigational product within 30 days or within 5 half-lives of the product (whichever is greater) before Day 1
•Vaccination within 30 days before Day 1, or planned vaccination during the study

Outcomes

Primary Outcomes

Percentage of subjects with TEAEs by severity by Cohort

Time Frame: Up to 32 days after start of CSL889 infusion

Percentage of subjects with TEAEs by causality by Cohort

Time Frame: Up to 32 days after start of CSL889 infusion

Percentage of subjects with treatment-emergent adverse events (TEAEs) by Cohort

Time Frame: Up to 32 days after start of CSL889 infusion

Secondary Outcomes

Clearance (CL) of CSL889 by Cohort(Up to 32 days after CSL889 infusion)
Maximum observed serum concentration (Cmax) of CSL889 by Cohort(Up to 32 days after CSL889 infusion)
Area under CSL889 serum concentration-time curve (AUC) from time 0 to time t (AUC0-t) by Cohort(Up to 32 days after CSL889 infusion)
Time of Cmax (tmax) of CSL889 by Cohort(Up to 32 days after CSL889 infusion)
Volume of distribution (Vz) of CSL889 by Cohort(Up to 32 days after CSL889 infusion)
Maximum observed serum concentration (Cmax) of CSL889 by Cohort AUC extrapolated to infinity (AUC0-inf) by CSL889 dose level(Up to 32 days after CSL889 infusion)
Terminal half-life (t1/2) of CSL889 by Cohort(Up to 32 days after CSL889 infusion)
Percentage of subjects with detectable antibodies to CSL889 by Cohort(Up to 32 days after CSL889 infusion)