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CSL200 Gene Therapy in Adults With Severe Sickle Cell Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04091737
Recruitment Status : Terminated (Unanticipated delays, not for safety reasons)
First Posted : September 17, 2019
Last Update Posted : June 18, 2021
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Study Description
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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.

Condition or disease Intervention/treatment Phase
Anemia, Sickle Cell Biological: Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 2, 2019
Actual Primary Completion Date : May 5, 2021
Actual Study Completion Date : May 5, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: CSL200
Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734
 Biological: Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734
  • 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
Other Name: CSL200


Outcome Measures
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Primary Outcome Measures :
  1. 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.


  2. Number of subjects experiencing AEs, SAEs, and AESIs associated with the administration of CSL200 [ Time Frame: Up to 48 weeks ]
  3. 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 ]
  4. 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 ]
  5. Number of AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan [ Time Frame: Up to 3 weeks ]
  6. Number of subjects experiencing AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan [ Time Frame: Up to 3 weeks ]

Secondary Outcome Measures :
  1. Total by-subject number of CD34+ HSPCs collected in total and in each apheresis session [ Time Frame: Up to 2 days ]
    Collection of CD34+ HSPCs by apheresis after mobilization with plerixafor assessed by CD34+ HSPCs collected

  2. Number of subjects receiving plerixafor and number of plerixafor doses administered by subject [ Time Frame: Up to 2 days ]
    Collection of CD34+ HSPCs by apheresis after mobilization with plerixafor assessed by plerixafor administrations

  3. Number of subjects undergoing apheresis and number of apheresis sessions by subject [ Time Frame: Up to 2 days ]
    Collection of CD34+ HSPCs by apheresis after mobilization with plerixafor assessed by apheresis sessions

  4. The number of subjects undergoing reduced intensity conditioning with melphalan and able to receive CSL200 [ Time Frame: 2 days ]
    Reduced intensity conditioning assessed by subjects receiving melphalan

  5. Number of subjects receiving CSL200 [ Time Frame: 1 day ]
  6. By-subject number of separate CSL200 drug products administered [ Time Frame: 1 day ]
  7. Number of CSL200 CD34+ HSPCs/kg administered by subject and by CSL200 drug product [ Time Frame: 1 day ]
  8. By-subject total number and percentage of CD34+ HSPCs transduced with CAL-H [ Time Frame: Up to 48 weeks ]
  9. Vector copy number (VCN) [ Time Frame: Up to 48 weeks ]
    VCN will be determined by using the average number of CAL-H vector genomes per cell


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

    1. ≥ 2 episodes of acute chest syndrome in the last 2 years.
    2. ≥ 3 episodes of severe pain events requiring a visit to a medical facility and treatment with opioids in the last 2 years.
    3. > 2 episodes of recurrent priapism in the last 2 years.
    4. Red-cell alloimmunization (> 2 antibodies) during long-term transfusion therapy (lifetime history).
    5. Chronic transfusions for primary or secondary prophylaxis (lifetime history).
    6. Trans-thoracic echocardiograph evidence of tricuspid valve regurgitant jet velocity ≥ 2.7 m/sec (lifetime history).
    7. 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:

    1. Absolute neutrophil count < 1000/µL.
    2. Platelet count < 120,000/µL.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04091737


Locations
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United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
CSL Behring
Investigators
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Study Director: Study Director CSL Behring
More Information
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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT04091737    
Other Study ID Numbers: CSL200_1001
First Posted: September 17, 2019    Key Record Dates
Last Update Posted: June 18, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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.
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
 Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn