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

NCT ID: NCT04285827

Last Updated: 2023-09-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-20

Study Completion Date

2023-07-24

Brief Summary

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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.

Detailed Description

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Conditions

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Sickle Cell Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CSL889 Cohort A1 (Dose 1)

CSL889 administered as a single IV infusion

Group Type EXPERIMENTAL

CSL889

Intervention Type BIOLOGICAL

Administered as an IV infusion

CSL889 Cohort A2 (Dose 2)

CSL889 administered as a single IV infusion

Group Type EXPERIMENTAL

CSL889

Intervention Type BIOLOGICAL

Administered as an IV infusion

CSL889 Cohort A3 (Dose 3)

CSL889 administered as a single IV infusion

Group Type EXPERIMENTAL

CSL889

Intervention Type BIOLOGICAL

Administered as an IV infusion

CSL889 Cohort A4 (Dose 4)

CSL889 administered as a single IV infusion

Group Type EXPERIMENTAL

CSL889

Intervention Type BIOLOGICAL

Administered as an IV infusion

CSL889 Cohort A5 (Dose 5)

CSL889 administered as a single IV infusion

Group Type EXPERIMENTAL

CSL889

Intervention Type BIOLOGICAL

Administered as an IV infusion

CSL889 Cohort A6 (Dose 6)

CSL889 administered as a single IV infusion

Group Type EXPERIMENTAL

CSL889

Intervention Type BIOLOGICAL

Administered as an IV infusion

CSL889 Cohort B1 (low dose)

CSL889 administered as a single IV infusion

Group Type EXPERIMENTAL

CSL889

Intervention Type BIOLOGICAL

Administered as an IV infusion

CSL889 Cohort B2 (high dose)

CSL889 administered as a single IV infusion

Group Type EXPERIMENTAL

CSL889

Intervention Type BIOLOGICAL

Administered as an IV infusion

Interventions

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CSL889

Administered as an IV infusion

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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CSL Behring

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

CSL Behring

Locations

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University of Illinois Hospital and Health Science Systems

Chicago, Illinois, United States

Site Status

The Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Jacobi Medical Center

The Bronx, New York, United States

Site Status

Brody School of Medicine at East Carolina University

Greenville, North Carolina, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Amsterdam UMC Academic Medical Center

Amsterdam, , Netherlands

Site Status

Erasmus University Medical Center

Rotterdam, , Netherlands

Site Status

Liverpool University Hospital

Liverpool, , United Kingdom

Site Status

Guys and St. Thomas

London, , United Kingdom

Site Status

University College London Hospital

London, , United Kingdom

Site Status

Manchester University Hospitals NHS Foundation Trust / Manchester Royal Infirmary

Manchester, , United Kingdom

Site Status

Early Phase Unit

Manchester, , United Kingdom

Site Status

Countries

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United States Netherlands United Kingdom

Other Identifiers

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2019-001870-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CSL889_1001

Identifier Type: -

Identifier Source: org_study_id

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