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

Sponsor
CSL Behring (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04285827
Collaborator
(none)
32
Enrollment
12
Locations
8
Arms
21.4
Anticipated Duration (Months)
2.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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
  • Biological: CSL889
 Phase 1

Study Design

Study Type:
Interventional
Anticipated 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
Anticipated Primary Completion Date :
Mar 1, 2023
Anticipated Study Completion Date :
Mar 1, 2023

Arms and Interventions

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

Primary Outcome Measures

  1. Percentage of subjects with treatment-emergent adverse events (TEAEs) by Cohort [Up to 32 days after start of CSL889 infusion]

  2. Percentage of subjects with TEAEs by severity by Cohort [Up to 32 days after start of CSL889 infusion]

  3. Percentage of subjects with TEAEs by causality by Cohort [Up to 32 days after start of CSL889 infusion]

Secondary Outcome Measures

  1. Maximum observed serum concentration (Cmax) of CSL889 by Cohort [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 [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 [Up to 32 days after CSL889 infusion]

  4. Time of Cmax (tmax) of CSL889 by Cohort [Up to 32 days after CSL889 infusion]

  5. Terminal half-life (t1/2) of CSL889 by Cohort [Up to 32 days after CSL889 infusion]

  6. Clearance (CL) of CSL889 by Cohort [Up to 32 days after CSL889 infusion]

  7. Volume of distribution (Vz) of CSL889 by Cohort [Up to 32 days after CSL889 infusion]

  8. Percentage of subjects with detectable antibodies to CSL889 by Cohort [Up to 32 days after CSL889 infusion]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 60 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 CSL889 infusion (Part A) or subject hospitalized for uncomplicated VOC (Part B)

  • 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:

  • 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.

  • 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

Locations

Site City State Country Postal Code
1 University of Illinois Hospital and Health Science Systems Chicago Illinois United States 60612
2 The Johns Hopkins Hospital Baltimore Maryland United States 21287
3 University of Minnesota Minneapolis Minnesota United States 55455
4 Brody School of Medicine at East Carolina University Greenville North Carolina United States 27834
5 Ohio State University Columbus Ohio United States 43201
6 Medical University of South Carolina Charleston South Carolina United States 29425
7 Amsterdam UMC Academic Medical Center Amsterdam Netherlands
8 Liverpool University Hospital Liverpool United Kingdom
9 Guys and St. Thomas London United Kingdom
10 University College London Hospital London United Kingdom
11 Manchester University Hospitals NHS Foundation Trust / Manchester Royal Infirmary Manchester United Kingdom M13 9WL
12 Early Phase Unit Manchester United Kingdom

Sponsors and Collaborators

  • CSL Behring

Investigators

  • Study Director: Study Director, CSL Behring

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
CSL Behring
ClinicalTrials.gov Identifier:
NCT04285827
Other Study ID Numbers:
  • CSL889_1001
  • 2019-001870-27
First Posted:
Feb 26, 2020
Last Update Posted:
Aug 12, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Anemia, Sickle Cell

Study Results

No Results Posted as of Aug 12, 2022