CSL200 Gene Therapy in Adults With Severe Sickle Cell Disease

• ClinicalTrials.gov Identifier: NCT04091737
• Recruitment Status: Terminated
• First Posted: September 17, 2019
• Last Update Posted: June 18, 2021
• Sponsor: CSL Behring
• Information provided by (Responsible Party): CSL Behring

Tracking Information

• First Submitted Date: September 13, 2019
• First Posted Date: September 17, 2019
• Last Update Posted Date: June 18, 2021
• Actual Study Start Date: October 2, 2019
• Actual Primary Completion Date: May 5, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 13, 2019)

• 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 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 13, 2019)

• 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
• 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
• 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
• 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
• 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 ]
  VCN will be determined by using the average number of CAL-H vector genomes per cell

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Anemia, Sickle Cell

Intervention

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

Study Arms

Experimental: CSL200

Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734

Intervention: Biological: Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human γ-globinG16D and short-hairpin RNA734

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 14, 2021): 1
• Original Estimated Enrollment (submitted: September 13, 2019): 3
• Actual Study Completion Date: May 5, 2021
• Actual Primary Completion Date: May 5, 2021 (Final data collection date for primary outcome measure)

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:

  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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04091737
• Other Study ID Numbers: CSL200_1001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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
• Supporting Materials: 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.

• Current Responsible Party: CSL Behring
• Original Responsible Party: Same as current
• Current Study Sponsor: CSL Behring
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Study Director; CSL Behring

• PRS Account: CSL Behring
• Verification Date: June 2021