Back to resultsCSL200 Gene Therapy in Adults With Severe Sickle Cell Disease
Primary Purpose
Anemia, Sickle Cell
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734
Sponsored by
About this trial
This is an interventional treatment trial for Anemia, Sickle Cell
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- City of Hope Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CSL200
Arm Description
Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734
Outcomes
Primary Outcome Measures
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.
Number of subjects experiencing AEs, SAEs, and AESIs associated with the administration of CSL200
Number of AEs, SAEs, and AESIs associated with the collection of CD34+ HSPCs by apheresis after mobilization with plerixafor
Number of subjects experiencing AEs, SAEs, and AESIs associated with the collection of CD34+ HSPCs by apheresis after mobilization with plerixafor
Number of AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan
Number of subjects experiencing AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan
Secondary Outcome Measures
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
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
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
The number of subjects undergoing reduced intensity conditioning with melphalan and able to receive CSL200
Reduced intensity conditioning assessed by subjects receiving melphalan
Number of subjects receiving CSL200
By-subject number of separate CSL200 drug products administered
Number of CSL200 CD34+ HSPCs/kg administered by subject and by CSL200 drug product
By-subject total number and percentage of CD34+ HSPCs transduced with CAL-H
Vector copy number (VCN)
VCN will be determined by using the average number of CAL-H vector genomes per cell
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04091737
Brief Title
CSL200 Gene Therapy in Adults With Severe Sickle Cell Disease
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Terminated
Why Stopped
Unanticipated delays, not for safety reasons
Study Start Date
October 2, 2019 (Actual)
Primary Completion Date
May 5, 2021 (Actual)
Study Completion Date
May 5, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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 melphalan, and administration of CSL200.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Sickle Cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CSL200
Arm Type
Experimental
Arm Description
Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734
Intervention Type
Biological
Intervention Name(s)
Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734
Other Intervention Name(s)
CSL200
Intervention Description
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
Primary Outcome Measure Information:
Title
Number of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) associated with the administration of CSL200
Description
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.
Time Frame
Up to 48 weeks
Title
Number of subjects experiencing AEs, SAEs, and AESIs associated with the administration of CSL200
Time Frame
Up to 48 weeks
Title
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
Title
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
Title
Number of AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan
Time Frame
Up to 3 weeks
Title
Number of subjects experiencing AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan
Time Frame
Up to 3 weeks
Secondary Outcome Measure Information:
Title
Total by-subject number of CD34+ HSPCs collected in total and in each apheresis session
Description
Collection of CD34+ HSPCs by apheresis after mobilization with plerixafor assessed by CD34+ HSPCs collected
Time Frame
Up to 2 days
Title
Number of subjects receiving plerixafor and number of plerixafor doses administered by subject
Description
Collection of CD34+ HSPCs by apheresis after mobilization with plerixafor assessed by plerixafor administrations
Time Frame
Up to 2 days
Title
Number of subjects undergoing apheresis and number of apheresis sessions by subject
Description
Collection of CD34+ HSPCs by apheresis after mobilization with plerixafor assessed by apheresis sessions
Time Frame
Up to 2 days
Title
The number of subjects undergoing reduced intensity conditioning with melphalan and able to receive CSL200
Description
Reduced intensity conditioning assessed by subjects receiving melphalan
Time Frame
2 days
Title
Number of subjects receiving CSL200
Time Frame
1 day
Title
By-subject number of separate CSL200 drug products administered
Time Frame
1 day
Title
Number of CSL200 CD34+ HSPCs/kg administered by subject and by CSL200 drug product
Time Frame
1 day
Title
By-subject total number and percentage of CD34+ HSPCs transduced with CAL-H
Time Frame
Up to 48 weeks
Title
Vector copy number (VCN)
Description
VCN will be determined by using the average number of CAL-H vector genomes per cell
Time Frame
Up to 48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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.
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing 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.
Learn more about this trial
CSL200 Gene Therapy in Adults With Severe Sickle Cell Disease
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