CSL200 Gene Therapy in Adults With Severe Sickle Cell Disease

CSL Behring

Status and phase: Terminated; Phase 1

Conditions: Anemia, Sickle Cell

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT04091737

CSL200_1001

Details and patient eligibility

About

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.

Enrollment: 1 patient

Sex: All

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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1 participants in 1 patient group

CSL200

Experimental group

Description:

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

Treatment:

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