Unanticipated delays, not for safety reasons

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.

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.

CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.

Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.

An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.

The requesting party must execute an appropriate data sharing agreement before IPD will be made available.