Safety of Single Doses of CSL889 in Adult Patients With Sickle Cell Disease
- Conditions
- Sickle Cell Disease
- Interventions
- Biological: CSL889
- Registration Number
- NCT04285827
- Lead Sponsor
- CSL Behring
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 28
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description CSL889 Cohort A1 (Dose 1) CSL889 CSL889 administered as a single IV infusion CSL889 Cohort A2 (Dose 2) CSL889 CSL889 administered as a single IV infusion CSL889 Cohort A4 (Dose 4) CSL889 CSL889 administered as a single IV infusion CSL889 Cohort B1 (low dose) CSL889 CSL889 administered as a single IV infusion CSL889 Cohort B2 (high dose) CSL889 CSL889 administered as a single IV infusion CSL889 Cohort A3 (Dose 3) CSL889 CSL889 administered as a single IV infusion CSL889 Cohort A5 (Dose 5) CSL889 CSL889 administered as a single IV infusion CSL889 Cohort A6 (Dose 6) CSL889 CSL889 administered as a single IV infusion
- Primary Outcome Measures
Name Time Method 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 Percentage of subjects with treatment-emergent adverse events (TEAEs) by Cohort Up to 32 days after start of CSL889 infusion
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (15)
Liverpool University Hospital
🇬🇧Liverpool, United Kingdom
The Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
University College London Hospital
🇬🇧London, United Kingdom
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Manchester University Hospitals NHS Foundation Trust / Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom
Guys and St. Thomas
🇬🇧London, United Kingdom
University of Illinois Hospital and Health Science Systems
🇺🇸Chicago, Illinois, United States
Early Phase Unit
🇬🇧Manchester, United Kingdom
Brody School of Medicine at East Carolina University
🇺🇸Greenville, North Carolina, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Amsterdam UMC Academic Medical Center
🇳🇱Amsterdam, Netherlands
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Erasmus University Medical Center
🇳🇱Rotterdam, Netherlands
Jacobi Medical Center
🇺🇸Bronx, New York, United States