Sickle Cell DiseasePhase 1NCT04285827
Safety of Single Doses of CSL889 in Adult Patients With Sickle Cell Disease
A Phase 1 study testing CSL889 in people with Sickle Cell Disease, run by CSL Behring at 15 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- CSL889
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 15 sitesin 3 countries
- Study dates
- 20 May 2021to 24 Jul 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
15 sites in 3 countries.
15 sites in 3 countries
United States8 sites
The Johns Hopkins Hospital
Baltimore, Maryland, 21287
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Illinois Hospital and Health Science Systems
Chicago, Illinois, 60612
Ohio State University
Columbus, Ohio, 43201
Brody School of Medicine at East Carolina University
Greenville, North Carolina, 27834
University of Minnesota
Minneapolis, Minnesota, 55455
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Jacobi Medical Center
The Bronx, New York, 10461
United Kingdom5 sites
Liverpool University Hospital
Liverpool
Guys and St. Thomas
London
University College London Hospital
London
Manchester University Hospitals NHS Foundation Trust / Manchester Royal Infirmary
Manchester, M13 9WL
Early Phase Unit
Manchester
Netherlands2 sites
Amsterdam UMC Academic Medical Center
Amsterdam
Erasmus University Medical Center
Rotterdam
About this study
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
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.
- Conditions
- Sickle Cell Disease
- Being tested
- CSL889
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CSL889Biological
Administered as an IV infusion
| Study group | Role | What they receive |
|---|---|---|
| CSL889 Cohort A1 (Dose 1) | Experimental | CSL889 administered as a single IV infusion Receives: Biological: CSL889 |
| CSL889 Cohort A2 (Dose 2) | Experimental | CSL889 administered as a single IV infusion Receives: Biological: CSL889 |
| CSL889 Cohort A3 (Dose 3) | Experimental | CSL889 administered as a single IV infusion Receives: Biological: CSL889 |
| CSL889 Cohort A4 (Dose 4) | Experimental | CSL889 administered as a single IV infusion Receives: Biological: CSL889 |
| CSL889 Cohort A5 (Dose 5) | Experimental | CSL889 administered as a single IV infusion Receives: Biological: CSL889 |
| CSL889 Cohort A6 (Dose 6) | Experimental | CSL889 administered as a single IV infusion Receives: Biological: CSL889 |
| CSL889 Cohort B1 (low dose) | Experimental | CSL889 administered as a single IV infusion Receives: Biological: CSL889 |
| CSL889 Cohort B2 (high dose) | Experimental | CSL889 administered as a single IV infusion Receives: Biological: CSL889 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of subjects with treatment-emergent adverse events (TEAEs) by Cohort
Measured: Up to 32 days after start of CSL889 infusion
Percentage of subjects with TEAEs by severity by Cohort
Measured: Up to 32 days after start of CSL889 infusion
Percentage of subjects with TEAEs by causality by Cohort
Measured: Up to 32 days after start of CSL889 infusion
Secondary outcomes (8)
Maximum observed serum concentration (Cmax) of CSL889 by Cohort
Measured: Up to 32 days after CSL889 infusion
Area under CSL889 serum concentration-time curve (AUC) from time 0 to time t (AUC0-t) by Cohort
Measured: Up to 32 days after CSL889 infusion
Maximum observed serum concentration (Cmax) of CSL889 by Cohort AUC extrapolated to infinity (AUC0-inf) by CSL889 dose level
Measured: Up to 32 days after CSL889 infusion
Time of Cmax (tmax) of CSL889 by Cohort
Measured: Up to 32 days after CSL889 infusion
Terminal half-life (t1/2) of CSL889 by Cohort
Measured: Up to 32 days after CSL889 infusion
Clearance (CL) of CSL889 by Cohort
Measured: Up to 32 days after CSL889 infusion
Volume of distribution (Vz) of CSL889 by Cohort
Measured: Up to 32 days after CSL889 infusion
Percentage of subjects with detectable antibodies to CSL889 by Cohort
Measured: Up to 32 days after CSL889 infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2020
- Study start20 May 2021
- Primary completion24 Jul 2023
- Study completion24 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by CSL BehringThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- CSL Behring
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, CSL Behring
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04285827
- Sponsor's protocol ID
- CSL889_1001
- Other IDs
- 2019-001870-27, 2019
- Status last verified
- Sep 2023
- First submitted
- 24 Feb 2020
- Last updated
- 6 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04285827
- Acronym / sponsor ID
- CSL889_1001
- Conditions
- Sickle Cell Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- CSL BehringIndustry (pharma, biotech, devices)
- Study start
- 20 May 2021 (actual)
- Primary completion
- 24 Jul 2023 (actual)
- Study completion
- 24 Jul 2023 (actual)
- First posted
- 26 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| CSL889 Cohort A1 (Dose 1) | Experimental | Biological: CSL889CSL889 administered as a single IV infusion |
| CSL889 Cohort A2 (Dose 2) | Experimental | Biological: CSL889CSL889 administered as a single IV infusion |
| CSL889 Cohort A3 (Dose 3) | Experimental | Biological: CSL889CSL889 administered as a single IV infusion |
| CSL889 Cohort A4 (Dose 4) | Experimental | Biological: CSL889CSL889 administered as a single IV infusion |
| CSL889 Cohort A5 (Dose 5) | Experimental | Biological: CSL889CSL889 administered as a single IV infusion |
| CSL889 Cohort A6 (Dose 6) | Experimental | Biological: CSL889CSL889 administered as a single IV infusion |
| CSL889 Cohort B1 (low dose) | Experimental | Biological: CSL889CSL889 administered as a single IV infusion |
| CSL889 Cohort B2 (high dose) | Experimental | Biological: CSL889CSL889 administered as a single IV infusion |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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):
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CSL889Administered as an IV infusion | Biological | CSL889 Cohort A1 (Dose 1), CSL889 Cohort A2 (Dose 2), CSL889 Cohort A3 (Dose 3), CSL889 Cohort A4 (Dose 4), CSL889 Cohort A5 (Dose 5), CSL889 Cohort A6 (Dose 6), CSL889 Cohort B1 (low dose), CSL889 Cohort B2 (high dose) |
Primary outcome
Percentage of subjects with treatment-emergent adverse events (TEAEs) by Cohort
Time frame: Up to 32 days after start of CSL889 infusion
Percentage of subjects with TEAEs by severity by Cohort
Time frame: Up to 32 days after start of CSL889 infusion
Percentage of subjects with TEAEs by causality by Cohort
Time frame: Up to 32 days after start of CSL889 infusion
8 secondary outcomes
Maximum observed serum concentration (Cmax) of CSL889 by Cohort
Time frame: Up to 32 days after CSL889 infusion
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
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
Time of Cmax (tmax) of CSL889 by Cohort
Time frame: Up to 32 days after CSL889 infusion
Terminal half-life (t1/2) of CSL889 by Cohort
Time frame: Up to 32 days after CSL889 infusion
Clearance (CL) of CSL889 by Cohort
Time frame: Up to 32 days after CSL889 infusion
Volume of distribution (Vz) of CSL889 by Cohort
Time frame: Up to 32 days after CSL889 infusion
Percentage of subjects with detectable antibodies to CSL889 by Cohort
Time frame: Up to 32 days after CSL889 infusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2023.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
CSL Behring
15 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CSL889 in people with Sickle Cell Disease, run by CSL Behring at 15 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, United Kingdom, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of subjects with treatment-emergent adverse events (TEAEs) by Cohort (time frame: Up to 32 days after start of CSL889 infusion). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2023.