Safety of Single Ascending Doses of CSL889 in Adult Patients With Stable Sickle Cell Disease
Safety of Single Ascending Doses of CSL889 in Adult Patients With Stable Sickle Cell Disease
This is a phase 1, first-in-human, multi-center, open-label, single ascending dose (SAD)
 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 stable sickle cell disease (SCD). The study involves
 sequential dose escalation of cohorts with between-group assessments of key safety and PK
 variables.
Inclusion Criteria:

 -  Diagnosis of SCD characterized by HbSS or SCD characterized by the compound
 heterozygous state of the βS mutation with β0 thalassemia mutations (HbSβ0)

 -  Aged 18 to 60 years, inclusive

 -  Stable SCD for at least 30 days before Day 1

 -  Subject is either not taking hydroxyurea and / or L-glutamine, or subject has been
 taking hydroxyurea and / or L-glutamine for at least 30 days before Day 1 on a stable,
 well tolerated regimen that is planned to continue without change throughout the study

 Exclusion Criteria:

 -  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.

 -  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