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

About the study

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.

Study point of contact

Trial Registration Coordinator
610-878-4000
[email protected]

Locations

6 United States sites

5 United Kingdom sites

1 Netherlands site

Age

18 Years - 60 Years

Phase

Phase 1

Study type

Interventional

Gender

All

Interventions

Biological

participation requirements

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

participation restrictions

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

Locations

  • Chicago, Illinois, United States, University of Illinois Hospital and Health Science Systems
  • Baltimore, Maryland, United States, The Johns Hopkins Hospital
  • Minneapolis, Minnesota, United States, University of Minnesota
  • Greenville, North Carolina, United States, Brody School of Medicine at East Carolina University
  • Columbus, Ohio, United States, Ohio State University
  • Charleston, South Carolina, United States, Medical University of South Carolina
  • Amsterdam, Netherlands, Amsterdam UMC Academic Medical Center
  • Liverpool, United Kingdom, Liverpool University Hospital
  • London, United Kingdom, Guys and St. Thomas
  • London, United Kingdom, University College London Hospital
  • Manchester, United Kingdom, Manchester University Hospitals NHS Foundation Trust / Manchester Royal Infirmary
  • Manchester, United Kingdom, Early Phase Unit
Last updated 2022-09-02