CSL200 Gene Therapy in Adults With Severe Sickle Cell Disease

NCT ID: NCT04091737

Last Updated: 2021-06-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-02
• Study Completion Date: 2021-05-05

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CSL200

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

Group Type: EXPERIMENTAL

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

Intervention Type: 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

Interventions

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

Intervention Type: BIOLOGICAL

Other Intervention Names

CSL200

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CSL Behring

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

CSL Behring

Locations

City of Hope Medical Center

Duarte, California, United States

Countries

United States

Other Identifiers

CSL200_1001

Identifier Type: -

Identifier Source: org_study_id