CSL200 Gene Therapy in Adults With Severe Sickle Cell Disease

Anemia, Sickle Cell Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04091737
• Other study ID #: CSL200_1001
• Status: Terminated
• Phase: Phase 1
• Start date: October 2, 2019
• Est. completion date: May 5, 2021

Study information

• Verified date: June 2021
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: May 5, 2021
• Est. primary completion date: May 5, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Diagnosis of sickle cell disease with the homozygous HbS homozygous genotype (HbSS) or an HbSß thalassemia variant (ie, HbSß0 thalassemia or HbSß+ 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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell

Intervention

Biological:
• Autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human ?-globinG16D and short-hairpin RNA734
Cryopreserved formulated autologous enriched CD34+ cell fraction that contains CD34+ cells transduced with lentiviral vector encoding human ?-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

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of subjects experiencing AEs, SAEs, and AESIs associated with the administration of CSL200		Up to 48 weeks
Primary	Number of AEs, SAEs, and AESIs associated with the collection of CD34+ HSPCs by apheresis after mobilization with plerixafor		Up to 6 weeks
Primary	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
Primary	Number of AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan		Up to 3 weeks
Primary	Number of subjects experiencing AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan		Up to 3 weeks
Secondary	Total by-subject number of CD34+ HSPCs collected in total and in each apheresis session	Collection of CD34+ HSPCs by apheresis after mobilization with plerixafor assessed by CD34+ HSPCs collected	Up to 2 days
Secondary	Number of subjects receiving plerixafor and number of plerixafor doses administered by subject	Collection of CD34+ HSPCs by apheresis after mobilization with plerixafor assessed by plerixafor administrations	Up to 2 days
Secondary	Number of subjects undergoing apheresis and number of apheresis sessions by subject	Collection of CD34+ HSPCs by apheresis after mobilization with plerixafor assessed by apheresis sessions	Up to 2 days
Secondary	The number of subjects undergoing reduced intensity conditioning with melphalan and able to receive CSL200	Reduced intensity conditioning assessed by subjects receiving melphalan	2 days
Secondary	Number of subjects receiving CSL200		1 day
Secondary	By-subject number of separate CSL200 drug products administered		1 day
Secondary	Number of CSL200 CD34+ HSPCs/kg administered by subject and by CSL200 drug product		1 day
Secondary	By-subject total number and percentage of CD34+ HSPCs transduced with CAL-H		Up to 48 weeks
Secondary	Vector copy number (VCN)	VCN will be determined by using the average number of CAL-H vector genomes per cell	Up to 48 weeks