A 2-Part, Phase 1, Multicenter, Single Dose, Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CSL889 in Adult Patients with Sickle Cell Disease
- Conditions
- Sickle cell disease10005330
- Registration Number
- NL-OMON52183
- Lead Sponsor
- CSL Behring LLC
- Brief Summary
Trial is onging in other countries
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 5
• 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):
o Fever (> 38.5 °C)
o Hypotension (< 90/60 mmHg)
o Hypoxia (< 90% oxygen saturation on room air, or requiring oxygen therapy to
maintain oxygen saturation above 90%)
o New neurological signs and / or symptoms clinically suggestive of stroke or
transient ischemic attack
o 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
• Hospitalization for vaso-occlusive crisis (VOC) or treated with parenteral
pain medications in other medical settings such as the emergency department or
day hospital for VOC during the past 30 days before Day 1
• Blood transfusion within the 90 days before Day 1, or expecting blood
transfusion during the study
• 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
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoints:<br /><br>Frequency, nature and severity of TEAEs from start of infusion until 32 days<br /><br>after infusion in subjects with stable SCD and in subjects with SCD in VOC</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints:<br /><br>1. Serum PK parameters of CSL889, with and without adjustment for baseline<br /><br>hemopexin: Cmax, AUC from time 0 to the last measurable concentration<br /><br>(AUC0-last), AUC0-inf, time of maximum concentration (tmax), terminal half-life<br /><br>(t1/2), clearance (CL), volume of distribution during the elimination phase (Vz)<br /><br>2. Anti-CSL889 antibodies</p><br>