CSL200 Gene Therapy in Adults With Severe Sickle Cell Disease

NCT04091737 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: CSL200_1001
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Anemia, Sickle Cell

Outcome Measures

Primary Outcomes (6)

• 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.

  Up to 48 weeks

• Number of subjects experiencing AEs, SAEs, and AESIs associated with the administration of CSL200

  Up to 48 weeks

• Number of AEs, SAEs, and AESIs associated with the collection of CD34+ HSPCs by apheresis after mobilization with plerixafor

  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

  Up to 6 weeks

• Number of AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan

  Up to 3 weeks

• Number of subjects experiencing AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan

  Up to 3 weeks

Secondary Outcomes (9)

• Total by-subject number of CD34+ HSPCs collected in total and in each apheresis session

  Up to 2 days

• Number of subjects receiving plerixafor and number of plerixafor doses administered by subject

  Up to 2 days

• Number of subjects undergoing apheresis and number of apheresis sessions by subject

  Up to 2 days

• The number of subjects undergoing reduced intensity conditioning with melphalan and able to receive CSL200

  2 days

• Number of subjects receiving CSL200

  1 day

Study Arms (1)

CSL200

EXPERIMENTAL

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

Interventions

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

* 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

Also known as: CSL200

CSL200

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Study Director

  CSL Behring

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2019
• First Posted: September 17, 2019
• Study Start: October 2, 2019
• Primary Completion: May 5, 2021
• Study Completion: May 5, 2021
• Last Updated: June 18, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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.

Locations

US (1)