Long-term Follow-up of Subjects with Sickle Cell Disease Treated with Ex Vivo Gene Therapy

Long-term Follow-up of Subjects with Sickle Cell Disease Treated with Ex Vivo Gene Therapy Using Autologous Hematopoietic Stem Cells Transduced with a Lentiviral Vector

This is a multi-center, long-term safety and efficacy follow-up study for subjects with sickle cell disease who have been treated with ex vivo gene therapy drug product in bluebird bio-sponsored clinical studies. After completing the parent clinical study (approximately 2 years), eligible subjects will be followed for an additional 13 years for a total of 15 years post-drug product infusion. No investigational drug product will be administered in the study.

Study Overview

• Status: Enrolling by invitation
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Other: Safety and efficacy assessments

• Study Type: Observational
• Enrollment (Estimated): 85

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hospital Necker
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital Oakland
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611-2991
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Warren Grant Magnuson Clinical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota Masonic Children's Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New Hyde Park, New York, United States, 11040
      • Cohen Children's Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • The University of North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 53 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects with sickle cell disease treated with ex vivo gene therapy product in bluebird bio-sponsored clinical studies

Description

Inclusion Criteria:

• Provision of written informed consent for this study by subject, or as applicable, subject's parent(s)/legal guardian(s)
• Treated with drug product for therapy of sickle cell disease in a bluebird bio-sponsored clinical study

Exclusion Criteria:

• There are no exclusion criteria for this study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Subjects with sickle-cell disease; Subjects treated with ex vivo gene therapy drug product for sickle cell disease in a bluebird bio-sponsored study who agree to participate in this long-term follow-up study	Other: Safety and efficacy assessments; Safety evaluations, disease-specific assessments, and assessments to monitor for long-term complications of autologous transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with immune-related AEs (e.g., autoimmune disorders, GVHD, opportunistic infections, HIV)	Through 15 years post-drug product infusion
Number of subjects with new or worsening hematologic disorders	Through 15 years post-drug product infusion
Number of subjects with new or worsening neurologic disorders	Through 15 years post-drug product infusion
Number of subjects with malignancies	Through 15 years post-drug product infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with complete resolution of severe VOEs (sVOE-CR) over time through Year 15		Through 15 years post-drug product infusion
Proportion of subjects with complete resolution of VOEs (VOE-CR) over time through Year 15		Through 15 years post-drug product infusion
Annualized number of severe VOEs over time through Year 15		Through 15 years post-drug product infusion
Annualized number of VOEs over time through Year 15		Through 15 years post-drug product infusion
Change from parent study baseline in annualized number of severe VOEs over time through Year 15		Through 15 years post-drug product infusion
Assessment of total Hb over time post-drug product infusion through Year 15		Through 15 years post-drug product infusion
Assessment of non-transfused total Hb over time post-drug product infusion through Year 15	Non-transfused total Hb refers to the total g/dL of HbS + HbF + HbA2 + HbAT87Q	Through 15 years post-drug product infusion
Assessment of HbS percentage of non-transfused total Hb over time post-drug product infusion through Year 15	Non-transfused total Hb refers to the total g/dL of HbS + HbF + HbA2 + HbAT87Q	Through 15 years post-drug product infusion
Assessment of HbAT87Q percentage of non-transfused total Hb over time post-drug product infusion through Year 15	Non-transfused total Hb refers to the total g/dL of HbS + HbF + HbA2 + HbAT87Q	Through 15 years post-drug product infusion
Assessment of non-HbS percentage of non-transfused total Hb over time post-drug product infusion through Year 15	Non-transfused total Hb refers to the total g/dL of HbS + HbF + HbA2 + HbAT87Q. Non-HbS is the total g/dL of HbF + HbA2 + HbAT87Q	Through 15 years post-drug product infusion
Change from parent study baseline through Year 15 in hemolysis markers	Change from parent study baseline through Year 15 in absolute reticulocyte count, percent reticulocytes/erythrocytes, total bilirubin, indirect bilirubin, haptoglobin, and lactate dehydrogenase hemolysis markers	Through 15 years post-drug product infusion
Change from parent study baseline through Year 15 in markers of iron stores	Change from parent study baseline through Year 15 in serum ferritin and liver iron content markers of iron stores	15 years post-drug product infusion

Collaborators and Investigators

• Sponsor: bluebird bio
• Investigators: Study Director: Anjulika Chawla, MD, bluebird bio, Inc.

Publications and helpful links

General Publications

• Magrin E, Semeraro M, Hebert N, Joseph L, Magnani A, Chalumeau A, Gabrion A, Roudaut C, Marouene J, Lefrere F, Diana JS, Denis A, Neven B, Funck-Brentano I, Negre O, Renolleau S, Brousse V, Kiger L, Touzot F, Poirot C, Bourget P, El Nemer W, Blanche S, Treluyer JM, Asmal M, Walls C, Beuzard Y, Schmidt M, Hacein-Bey-Abina S, Asnafi V, Guichard I, Poiree M, Monpoux F, Touraine P, Brouzes C, de Montalembert M, Payen E, Six E, Ribeil JA, Miccio A, Bartolucci P, Leboulch P, Cavazzana M. Long-term outcomes of lentiviral gene therapy for the beta-hemoglobinopathies: the HGB-205 trial. Nat Med. 2022 Jan;28(1):81-88. doi: 10.1038/s41591-021-01650-w. Epub 2022 Jan 24.

Helpful Links

• HGB-205 Clinicaltrials.gov
• HGB-206 Clinicaltrials.gov
• HGB-210 Clinicaltrials.gov

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2020
• Primary Completion (Estimated): January 1, 2038
• Study Completion (Estimated): January 1, 2038

Study Registration Dates

• First Submitted: November 5, 2020
• First Submitted That Met QC Criteria: November 12, 2020
• First Posted (Actual): November 13, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 19, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Hematopoietic Stem Cells
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: LTF-307; 2019-004266-18 (EudraCT Number); 2024-513901-30-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Bluebird bio is committed to transparency. Appropriately de-identified patient-level datasets and supporting documents may be shared (if contractually or otherwise legally permitted) following study completion and once all applicable regulatory submissions based on this study have been performed. Sharing of individual patient data will be done according to criteria established by bluebird bio and/or industry best practices to protect confidential information and maintain the privacy of study participants. For inquiries, please contact us at datasharing@bluebirdbio.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No