Clinical trial NCT04091737: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Anemia, Sickle Cell
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2019-09-17
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) associated with the administration of CSL200
timeFrame: Up to 48 weeks
measure: Number of subjects experiencing AEs, SAEs, and AESIs associated with the administration of CSL200
timeFrame: Up to 48 weeks
measure: Number of AEs, SAEs, and AESIs associated with the collection of CD34+ HSPCs by apheresis after mobilization with plerixafor
timeFrame: Up to 6 weeks
measure: Number of subjects experiencing AEs, SAEs, and AESIs associated with the collection of CD34+ HSPCs by apheresis after mobilization with plerixafor
timeFrame: Up to 6 weeks
measure: Number of AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan
timeFrame: Up to 3 weeks
measure: Number of subjects experiencing AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan
timeFrame: Up to 3 weeks
Secondary outcomes:
measure: Total by-subject number of CD34+ HSPCs collected in total and in each apheresis session
timeFrame: Up to 2 days
measure: Number of subjects receiving plerixafor and number of plerixafor doses administered by subject
timeFrame: Up to 2 days
measure: Number of subjects undergoing apheresis and number of apheresis sessions by subject
timeFrame: Up to 2 days
measure: The number of subjects undergoing reduced intensity conditioning with melphalan and able to receive CSL200
timeFrame: 2 days
measure: Number of subjects receiving CSL200
timeFrame: 1 day
measure: By-subject number of separate CSL200 drug products administered
timeFrame: 1 day
measure: Number of CSL200 CD34+ HSPCs/kg administered by subject and by CSL200 drug product
timeFrame: 1 day
measure: By-subject total number and percentage of CD34+ HSPCs transduced with CAL-H
timeFrame: Up to 48 weeks
measure: Vector copy number (VCN)
timeFrame: Up to 48 weeks
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
Study officials:
affiliation: CSL Behring
name: Study Director
role: STUDY_DIRECTOR
References: