Safety of Single Doses of CSL889 in Adult Patients With Sickle Cell Disease

Sickle Cell Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04285827
• Other study ID #: CSL889_1001
• Secondary ID: 2019-001870-27
• Status: Completed
• Phase: Phase 1
• Start date: May 20, 2021
• Est. completion date: July 24, 2023

Study information

• Verified date: September 2023
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: July 24, 2023
• Est. primary completion date: July 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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 1. 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)
• Subject is either not taking one of the study permitted SCD therapies (hydroxyurea, L-glutamine, L-glutaminecrizanlizumab, and/or voxelotor) or subject has been taking one or more of those for at least 30 days before Day 1 and is on a stable, well tolerated regimen that is planned to continue without change throughout the study

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 CSL889.
• Treatment with any other drug / biologic that is newly approved for SCD during the conduct of this study within 90 days before Day 1. 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
• Body-mass index < 16 kg/m2 or weight < 50 kg (110 lbs)
• History of anaphylactic-type reactions, transfusion related reaction, asthma, or autoimmune disease

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Biological:
• CSL889
Administered as an IV infusion

Locations

Country	Name	City	State
Netherlands	Amsterdam UMC Academic Medical Center	Amsterdam
Netherlands	Erasmus University Medical Center	Rotterdam
United Kingdom	Liverpool University Hospital	Liverpool
United Kingdom	Guys and St. Thomas	London
United Kingdom	University College London Hospital	London
United Kingdom	Early Phase Unit	Manchester
United Kingdom	Manchester University Hospitals NHS Foundation Trust / Manchester Royal Infirmary	Manchester
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	Jacobi Medical Center	Bronx	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Illinois Hospital and Health Science Systems	Chicago	Illinois
United States	Ohio State University	Columbus	Ohio
United States	Brody School of Medicine at East Carolina University	Greenville	North Carolina
United States	University of Minnesota	Minneapolis	Minnesota
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of subjects with treatment-emergent adverse events (TEAEs) by Cohort		Up to 32 days after start of CSL889 infusion
Primary	Percentage of subjects with TEAEs by severity by Cohort		Up to 32 days after start of CSL889 infusion
Primary	Percentage of subjects with TEAEs by causality by Cohort		Up to 32 days after start of CSL889 infusion
Secondary	Maximum observed serum concentration (Cmax) of CSL889 by Cohort		Up to 32 days after CSL889 infusion
Secondary	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
Secondary	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
Secondary	Time of Cmax (tmax) of CSL889 by Cohort		Up to 32 days after CSL889 infusion
Secondary	Terminal half-life (t1/2) of CSL889 by Cohort		Up to 32 days after CSL889 infusion
Secondary	Clearance (CL) of CSL889 by Cohort		Up to 32 days after CSL889 infusion
Secondary	Volume of distribution (Vz) of CSL889 by Cohort		Up to 32 days after CSL889 infusion
Secondary	Percentage of subjects with detectable antibodies to CSL889 by Cohort		Up to 32 days after CSL889 infusion