Clinical trial NCT04285827: Safety of Single Doses of CSL889 in Adult Patients With Sickle Cell Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sickle Cell Disease
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2020-02-26
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of subjects with treatment-emergent adverse events (TEAEs) by Cohort
timeFrame: Up to 32 days after start of CSL889 infusion
measure: Percentage of subjects with TEAEs by severity by Cohort
timeFrame: Up to 32 days after start of CSL889 infusion
measure: Percentage of subjects with TEAEs by causality by Cohort
timeFrame: Up to 32 days after start of CSL889 infusion
Secondary outcomes:
measure: Maximum observed serum concentration (Cmax) of CSL889 by Cohort
timeFrame: Up to 32 days after CSL889 infusion
measure: Area under CSL889 serum concentration-time curve (AUC) from time 0 to time t (AUC0-t) by Cohort
timeFrame: Up to 32 days after CSL889 infusion
measure: Maximum observed serum concentration (Cmax) of CSL889 by Cohort AUC extrapolated to infinity (AUC0-inf) by CSL889 dose level
timeFrame: Up to 32 days after CSL889 infusion
measure: Time of Cmax (tmax) of CSL889 by Cohort
timeFrame: Up to 32 days after CSL889 infusion
measure: Terminal half-life (t1/2) of CSL889 by Cohort
timeFrame: Up to 32 days after CSL889 infusion
measure: Clearance (CL) of CSL889 by Cohort
timeFrame: Up to 32 days after CSL889 infusion
measure: Volume of distribution (Vz) of CSL889 by Cohort
timeFrame: Up to 32 days after CSL889 infusion
measure: Percentage of subjects with detectable antibodies to CSL889 by Cohort
timeFrame: Up to 32 days after CSL889 infusion
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois Hospital and Health Science Systems
state: Illinois
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Greenville
country: United States
facility: Brody School of Medicine at East Carolina University
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC Academic Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center
city: Liverpool
country: United Kingdom
facility: Liverpool University Hospital
city: London
country: United Kingdom
facility: Guys and St. Thomas
city: London
country: United Kingdom
facility: University College London Hospital
city: Manchester
country: United Kingdom
facility: Manchester University Hospitals NHS Foundation Trust / Manchester Royal Infirmary
city: Manchester
country: United Kingdom
facility: Early Phase Unit
Study officials:
affiliation: CSL Behring
name: Study Director
role: STUDY_DIRECTOR
References: