October, 10 2019

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

Locations

1 United States site

Age

18 to 45 Years

Genotypes

SS

Phase

Phase 1

About the study

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.

Study Type

Interventional

Phase

Phase 1

Age

18 to 45 Years

Genotype

SS

Gender

All

Inclusion Criteria

– Diagnosis of sickle cell disease with the homozygous 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.

Exclusion Criteria

– Hypoxanthine-guanine phosphoribosyl transferase (HPRT) deficiency.

– Thiopurine S-methyltransferase (TPMT) deficiency.

– Alpha thalassemia.

– Serum ferritin ≥ 2500 ng/mL.

– Inadequate bone marrow function, defined as at least 1 of the following:

1. Absolute neutrophil count < 1000/µL. 2. Platelet count < 120,000/µL.

Interventions

  • Biological

Outcome measures

  • Number of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) associated with the administration of CSL200
  • Number of AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan
  • Number of AEs, SAEs, and AESIs associated with the collection of CD34+ HSPCs by apheresis after mobilization with plerixafor
  • Number of subjects experiencing AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan
  • Number of subjects experiencing AEs, SAEs, and AESIs associated with the administration of CSL200
  • Number of subjects experiencing AEs, SAEs, and AESIs associated with the collection of CD34+ HSPCs by apheresis after mobilization with plerixafor

Location

  • City of Hope Medical Center, Duarte, California, United States, 91010 [Recruiting]

Contact Research Team

  • Trial Registration Coordinator
    610-878-4000

More info

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