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Safety of Single Doses of CSL889 in Adult Patients With Sickle Cell Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04285827
Recruitment Status : Recruiting
First Posted : February 26, 2020
Last Update Posted : March 14, 2023
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Study Description
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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.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Biological: CSL889 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 20, 2021
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : July 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: CSL889 Cohort A1 (Dose 1)
CSL889 administered as a single IV infusion
 Biological: CSL889
Administered as an IV infusion
Experimental: CSL889 Cohort A2 (Dose 2)
CSL889 administered as a single IV infusion
 Biological: CSL889
Administered as an IV infusion
Experimental: CSL889 Cohort A3 (Dose 3)
CSL889 administered as a single IV infusion
 Biological: CSL889
Administered as an IV infusion
Experimental: CSL889 Cohort A4 (Dose 4)
CSL889 administered as a single IV infusion
 Biological: CSL889
Administered as an IV infusion
Experimental: CSL889 Cohort A5 (Dose 5)
CSL889 administered as a single IV infusion
 Biological: CSL889
Administered as an IV infusion
Experimental: CSL889 Cohort A6 (Dose 6)
CSL889 administered as a single IV infusion
 Biological: CSL889
Administered as an IV infusion
Experimental: CSL889 Cohort B1 (low dose)
CSL889 administered as a single IV infusion
 Biological: CSL889
Administered as an IV infusion
Experimental: CSL889 Cohort B2 (high dose)
CSL889 administered as a single IV infusion
 Biological: CSL889
Administered as an IV infusion


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of subjects with treatment-emergent adverse events (TEAEs) by Cohort [ Time Frame: Up to 32 days after start of CSL889 infusion ]
  2. Percentage of subjects with TEAEs by severity by Cohort [ Time Frame: Up to 32 days after start of CSL889 infusion ]
  3. Percentage of subjects with TEAEs by causality by Cohort [ Time Frame: Up to 32 days after start of CSL889 infusion ]

Secondary Outcome Measures :
  1. Maximum observed serum concentration (Cmax) of CSL889 by Cohort [ Time Frame: Up to 32 days after CSL889 infusion ]
  2. Area under CSL889 serum concentration-time curve (AUC) from time 0 to time t (AUC0-t) by Cohort [ Time Frame: Up to 32 days after CSL889 infusion ]
  3. Maximum observed serum concentration (Cmax) of CSL889 by Cohort AUC extrapolated to infinity (AUC0-inf) by CSL889 dose level [ Time Frame: Up to 32 days after CSL889 infusion ]
  4. Time of Cmax (tmax) of CSL889 by Cohort [ Time Frame: Up to 32 days after CSL889 infusion ]
  5. Terminal half-life (t1/2) of CSL889 by Cohort [ Time Frame: Up to 32 days after CSL889 infusion ]
  6. Clearance (CL) of CSL889 by Cohort [ Time Frame: Up to 32 days after CSL889 infusion ]
  7. Volume of distribution (Vz) of CSL889 by Cohort [ Time Frame: Up to 32 days after CSL889 infusion ]
  8. Percentage of subjects with detectable antibodies to CSL889 by Cohort [ Time Frame: Up to 32 days after CSL889 infusion ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04285827


Contacts
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Contact: Trial Registration Coordinator 610-878-4000 clinicaltrials@cslbehring.com

Locations
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United States, Illinois
University of Illinois Hospital and Health Science Systems Recruiting
Chicago, Illinois, United States, 60612
Contact: Central Contact         
United States, Maryland
The Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Central Contact         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Central Contact         
United States, North Carolina
Brody School of Medicine at East Carolina University Recruiting
Greenville, North Carolina, United States, 27834
Contact: Central Contact         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43201
Contact: Central Contact         
United States, Pennsylvania
UPMC Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Central Contact         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Central Contact         
Netherlands
Amsterdam UMC Academic Medical Center Recruiting
Amsterdam, Netherlands
Contact: Central Contact         
Erasmus University Medical Center Recruiting
Rotterdam, Netherlands
Contact: Central Contact         
United Kingdom
Liverpool University Hospital Recruiting
Liverpool, United Kingdom
Contact: Central Contact         
Guys and St. Thomas Recruiting
London, United Kingdom
Contact: Central Contact         
University College London Hospital Recruiting
London, United Kingdom
Contact: Central Contact         
Manchester University Hospitals NHS Foundation Trust / Manchester Royal Infirmary Recruiting
Manchester, United Kingdom, M13 9WL
Contact: Central Contact         
Early Phase Unit Recruiting
Manchester, United Kingdom
Contact: Central Contact         
Sponsors and Collaborators
CSL Behring
Investigators
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Study Director: Study Director CSL Behring
More Information
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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT04285827    
Other Study ID Numbers: CSL889_1001
2019-001870-27 ( EudraCT Number )
First Posted: February 26, 2020    Key Record Dates
Last Update Posted: March 14, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.
Access Criteria:

Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.

An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.

The requesting party must execute an appropriate data sharing agreement before IPD will be made available.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
 Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn