Safety of Single Doses of CSL889 in Adult Patients With Sickle Cell Disease
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
2 other identifiers
interventional
28
3 countries
15
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started May 2021
Typical duration for phase_1
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 24, 2020
CompletedFirst Posted
Study publicly available on registry
February 26, 2020
CompletedStudy Start
First participant enrolled
May 20, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 24, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
July 24, 2023
CompletedSeptember 6, 2023
September 1, 2023
2.2 years
February 24, 2020
September 4, 2023
Conditions
Outcome Measures
Primary Outcomes (3)
Percentage of subjects with treatment-emergent adverse events (TEAEs) by Cohort
Up to 32 days after start of CSL889 infusion
Percentage of subjects with TEAEs by severity by Cohort
Up to 32 days after start of CSL889 infusion
Percentage of subjects with TEAEs by causality by Cohort
Up to 32 days after start of CSL889 infusion
Secondary Outcomes (8)
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
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
Time of Cmax (tmax) of CSL889 by Cohort
Up to 32 days after CSL889 infusion
Terminal half-life (t1/2) of CSL889 by Cohort
Up to 32 days after CSL889 infusion
- +3 more secondary outcomes
Study Arms (8)
CSL889 Cohort A1 (Dose 1)
EXPERIMENTALCSL889 administered as a single IV infusion
CSL889 Cohort A2 (Dose 2)
EXPERIMENTALCSL889 administered as a single IV infusion
CSL889 Cohort A3 (Dose 3)
EXPERIMENTALCSL889 administered as a single IV infusion
CSL889 Cohort A4 (Dose 4)
EXPERIMENTALCSL889 administered as a single IV infusion
CSL889 Cohort A5 (Dose 5)
EXPERIMENTALCSL889 administered as a single IV infusion
CSL889 Cohort A6 (Dose 6)
EXPERIMENTALCSL889 administered as a single IV infusion
CSL889 Cohort B1 (low dose)
EXPERIMENTALCSL889 administered as a single IV infusion
CSL889 Cohort B2 (high dose)
EXPERIMENTALCSL889 administered as a single IV infusion
Interventions
Administered as an IV infusion
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- CSL Behringlead
Study Sites (15)
University of Illinois Hospital and Health Science Systems
Chicago, Illinois, 60612, United States
The Johns Hopkins Hospital
Baltimore, Maryland, 21287, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Jacobi Medical Center
The Bronx, New York, 10461, United States
Brody School of Medicine at East Carolina University
Greenville, North Carolina, 27834, United States
Ohio State University
Columbus, Ohio, 43201, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Amsterdam UMC Academic Medical Center
Amsterdam, Netherlands
Erasmus University Medical Center
Rotterdam, Netherlands
Liverpool University Hospital
Liverpool, United Kingdom
Guys and St. Thomas
London, United Kingdom
University College London Hospital
London, United Kingdom
Manchester University Hospitals NHS Foundation Trust / Manchester Royal Infirmary
Manchester, M13 9WL, United Kingdom
Early Phase Unit
Manchester, United Kingdom
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Study Director
CSL Behring
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 24, 2020
First Posted
February 26, 2020
Study Start
May 20, 2021
Primary Completion
July 24, 2023
Study Completion
July 24, 2023
Last Updated
September 6, 2023
Record last verified: 2023-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.
- Access Criteria
- Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee. An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee. The requesting party must execute an appropriate data sharing agreement before IPD will be made available.
CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com. 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.