Anemia, Sickle CellPhase 1NCT04091737
CSL200 Gene Therapy in Adults With Severe Sickle Cell Disease
A Phase 1 study testing Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734 in people with Anemia, Sickle Cell, run by CSL Behring at 1 site in United States.
Trial summary
This is a phase 1 pilot study of CSL200 in adult subjects with severe sickle cell disease. The primary objectives of this study are to evaluate the safety of the following: collection of CD34+ hematopoietic stem / progenitor cells by apheresis after mobilization with plerixafor, reduced intensity conditioning with… Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Anemia, Sickle Cell
- What is being tested?
- Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Oct 2019to 5 May 2021
- 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 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of sickle cell disease with the homozygous HbS homozygous genotype (HbSS) or an HbSβ thalassemia variant (ie, HbSβ0 thalassemia or HbSβ+ thalassemia) genotype, confirmed by hemoglobin studies.
- Fetal hemoglobin (HbF) ≤ 15%.
- Severe sickle cell disease symptomatology, defined as any one or more of the following:
- ≥ 2 episodes of acute chest syndrome in the last 2 years.
- ≥ 3 episodes of severe pain events requiring a visit to a medical facility and treatment with opioids in the last 2 years.
- > 2 episodes of recurrent priapism in the last 2 years.
Show all 12Show fewer
- Red-cell alloimmunization (> 2 antibodies) during long-term transfusion therapy (lifetime history).
- Chronic transfusions for primary or secondary prophylaxis (lifetime history).
- Trans-thoracic echocardiograph evidence of tricuspid valve regurgitant jet velocity ≥ 2.7 m/sec (lifetime history).
- Clinically significant neurologic event (eg, ischemic stroke) or any neurological deficit lasting > 24 hours.
- Not eligible for human leukocyte antigen (HLA)-matched hematopoietic stem cell transplantation, defined as follows: no medically eligible, available, and willing 10/10 matched HLA-identical sibling donor, unless subject has declined this treatment option (as documented in the informed consent form).
- Not eligible for, declined, or, as judged by the investigator, failed therapy with hydroxyurea and if still on hydroxyurea is able to interrupt hydroxyurea starting at the beginning of the transfusions, before mobilization and apheresis.
Who cannot join
- Hypoxanthine-guanine phosphoribosyl transferase (HPRT) deficiency.
- Thiopurine S-methyltransferase (TPMT) deficiency.
- Alpha thalassemia.
- Inadequate bone marrow function, defined as at least 1 of the following:
- Absolute neutrophil count < 1000/µL.
- Platelet count < 120,000/µL.
Trial locations and contacts
1 site in 1 country.
United States1 site
City of Hope Medical Center
Duarte, California, 91010
About this study
Official title: A Phase 1 Pilot Study to Evaluate the Safety and Feasibility of Gene Therapy With CSL200 (Autologous Enriched CD34+ Cell Fraction That Contains CD34+ Cells Transduced With Lentiviral Vector Encoding Human γ-GlobinG16D and Short-Hairpin RNA734) in Adult Subjects With Severe Sickle Cell Disease
This is a phase 1 pilot study of CSL200 in adult subjects with severe sickle cell disease. The primary objectives of this study are to evaluate the safety of the following: collection of CD34+ hematopoietic stem / progenitor cells by apheresis after mobilization with plerixafor, reduced intensity conditioning with melphalan, and administration of CSL200.
- Conditions
- Anemia, Sickle Cell
- Being tested
- Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734
- 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.
Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734Biological
Also called CSL200
- Cryopreserved formulated autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734 in a bag for infusion
- Plerixafor to mobilize hematopoietic stem cells prior to each apheresis
- Single dose melphalan before administration of CSL200
| Study group | Role | What they receive |
|---|---|---|
| CSL200 | Experimental | Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734 Receives: Biological: Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) associated with the administration of CSL200
Adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or is medically significant.
Adverse event of special interest (AESI) is defined in this study as any of the following: acute immune reactions, autoimmunity to CSL200; malignancy; predominant integration site in presence of malignancy or other abnormality.
Measured: Up to 48 weeks
Number of subjects experiencing AEs, SAEs, and AESIs associated with the administration of CSL200
Measured: Up to 48 weeks
Number of AEs, SAEs, and AESIs associated with the collection of CD34+ HSPCs by apheresis after mobilization with plerixafor
Measured: Up to 6 weeks
Number of subjects experiencing AEs, SAEs, and AESIs associated with the collection of CD34+ HSPCs by apheresis after mobilization with plerixafor
Measured: Up to 6 weeks
Number of AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan
Measured: Up to 3 weeks
Number of subjects experiencing AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan
Measured: Up to 3 weeks
Secondary outcomes (9)
Total by-subject number of CD34+ HSPCs collected in total and in each apheresis session
Collection of CD34+ HSPCs by apheresis after mobilization with plerixafor assessed by CD34+ HSPCs collected
Measured: Up to 2 days
Number of subjects receiving plerixafor and number of plerixafor doses administered by subject
Collection of CD34+ HSPCs by apheresis after mobilization with plerixafor assessed by plerixafor administrations
Measured: Up to 2 days
Number of subjects undergoing apheresis and number of apheresis sessions by subject
Collection of CD34+ HSPCs by apheresis after mobilization with plerixafor assessed by apheresis sessions
Measured: Up to 2 days
The number of subjects undergoing reduced intensity conditioning with melphalan and able to receive CSL200
Reduced intensity conditioning assessed by subjects receiving melphalan
Measured: 2 days
Number of subjects receiving CSL200
Measured: 1 day
By-subject number of separate CSL200 drug products administered
Measured: 1 day
Number of CSL200 CD34+ HSPCs/kg administered by subject and by CSL200 drug product
Measured: 1 day
By-subject total number and percentage of CD34+ HSPCs transduced with CAL-H
Measured: Up to 48 weeks
Vector copy number (VCN)
VCN will be determined by using the average number of CAL-H vector genomes per cell
Measured: Up to 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2019
- Study start2 Oct 2019
- Primary completion5 May 2021
- Study completion5 May 2021
Why it stopped: Unanticipated delays, not for safety reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anemia, Sickle CellStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 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
- NCT04091737
- Sponsor's protocol ID
- CSL200_1001
- Status last verified
- Jun 2021
- First submitted
- 13 Sep 2019
- Last updated
- 18 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- 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 18 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Pilot Study to Evaluate the Safety and Feasibility of Gene Therapy With CSL200 (Autologous Enriched CD34+ Cell Fraction That Contains CD34+ Cells Transduced With Lentiviral Vector Encoding Human γ-GlobinG16D and Short-Hairpin RNA734) in Adult Subjects With Severe Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT04091737
- Acronym / sponsor ID
- CSL200_1001
- Conditions
- Anemia, Sickle Cell
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unanticipated delays, not for safety reasons
- Enrolment
- 1 participants (actual)
- Lead sponsor
- CSL BehringIndustry (pharma, biotech, devices)
- Study start
- 2 Oct 2019 (actual)
- Primary completion
- 5 May 2021 (actual)
- Study completion
- 5 May 2021 (actual)
- First posted
- 17 Sep 2019 (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 pilot study of CSL200 in adult subjects with severe sickle cell disease. The primary objectives of this study are to evaluate the safety of the following: collection of CD34+ hematopoietic stem / progenitor cells by apheresis after mobilization with plerixafor, reduced intensity conditioning with melphalan, and administration of CSL200.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CSL200 | Experimental | Biological: Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Diagnosis of sickle cell disease with the homozygous HbS homozygous genotype (HbSS) or an HbSβ thalassemia variant (ie, HbSβ0 thalassemia or HbSβ+ thalassemia) genotype, confirmed by hemoglobin studies.
- Fetal hemoglobin (HbF) ≤ 15%.
- Severe sickle cell disease symptomatology, defined as any one or more of the following:
- Not eligible for human leukocyte antigen (HLA)-matched hematopoietic stem cell transplantation, defined as follows: no medically eligible, available, and willing 10/10 matched HLA-identical sibling donor, unless subject has declined this treatment option (as documented in the informed consent form).
- Not eligible for, declined, or, as judged by the investigator, failed therapy with hydroxyurea and if still on hydroxyurea is able to interrupt hydroxyurea starting at the beginning of the transfusions, before mobilization and apheresis.
Key exclusion criteria (6 listed)
- Hypoxanthine-guanine phosphoribosyl transferase (HPRT) deficiency.
- Thiopurine S-methyltransferase (TPMT) deficiency.
- Alpha thalassemia.
- Inadequate bone marrow function, defined as at least 1 of the following:
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 |
|---|---|---|
| Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734Also: CSL200* Cryopreserved formulated autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734 in a bag for infusion * Plerixafor to mobilize hematopoietic stem cells prior to each apheresis * Single dose melphalan before administration of CSL200 | Biological | CSL200 |
Primary outcome
Number of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) associated with the administration of CSL200
Time frame: Up to 48 weeks
Adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or is medically significant. Adverse event of special interest (AESI) is defined in this study as any of the following: acute immune reactions, autoimmunity to CSL200; malignancy; predominant integration site in presence of malignancy or other abnormality.
Number of subjects experiencing AEs, SAEs, and AESIs associated with the administration of CSL200
Time frame: Up to 48 weeks
Number of AEs, SAEs, and AESIs associated with the collection of CD34+ HSPCs by apheresis after mobilization with plerixafor
Time frame: Up to 6 weeks
Number of subjects experiencing AEs, SAEs, and AESIs associated with the collection of CD34+ HSPCs by apheresis after mobilization with plerixafor
Time frame: Up to 6 weeks
Number of AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan
Time frame: Up to 3 weeks
Number of subjects experiencing AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan
Time frame: Up to 3 weeks
9 secondary outcomes
Total by-subject number of CD34+ HSPCs collected in total and in each apheresis session
Time frame: Up to 2 days
Number of subjects receiving plerixafor and number of plerixafor doses administered by subject
Time frame: Up to 2 days
Number of subjects undergoing apheresis and number of apheresis sessions by subject
Time frame: Up to 2 days
The number of subjects undergoing reduced intensity conditioning with melphalan and able to receive CSL200
Time frame: 2 days
Number of subjects receiving CSL200
Time frame: 1 day
By-subject number of separate CSL200 drug products administered
Time frame: 1 day
Number of CSL200 CD34+ HSPCs/kg administered by subject and by CSL200 drug product
Time frame: 1 day
By-subject total number and percentage of CD34+ HSPCs transduced with CAL-H
Time frame: Up to 48 weeks
Vector copy number (VCN)
Time frame: Up to 48 weeks
Results and safety
The study was stopped early (reason given: Unanticipated delays, not for safety reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2021.
- 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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734 in people with Anemia, Sickle Cell, run by CSL Behring at 1 site in United States.
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 12 inclusion and 6 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: stopped early, as of the sponsor's last update on 18 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 was stopped early (reason given: Unanticipated delays, not for safety reasons). Results are not available in the source record.
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?
Number of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) associated with the administration of CSL200 (time frame: Up to 48 weeks). The study lists 6 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 18 Jun 2021.