A Study Evaluating the Safety and Efficacy of the LentiGlobin BB305 Drug Product in β-Thalassemia Major Participants

NCT ID: NCT01745120

Last Updated: 2019-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2018-02-21

Brief Summary

This is a non-randomized, open label, multi-site, single-dose, phase 1/2 study in up to 18 participants (including at least 3 adolescents between 12 and 17 years of age, inclusive) with β-thalassemia major. The study will evaluate the safety and efficacy of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product [autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human βA-T87Q-globin gene].

Detailed Description

Subject participation for this study will be 2 years. Subjects who enroll in this study will be asked to participate in a subsequent long-term follow up study that will monitor the safety and efficacy of the treatment they receive for up to 13 years post-transplant.

Conditions

β-thalassemia Major

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LentiGlobin BB305 Drug Product

Group Type: EXPERIMENTAL

LentiGlobin BB305 Drug Product

Intervention Type: GENETIC

Transplant of autologous hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector.

Interventions

LentiGlobin BB305 Drug Product

Transplant of autologous hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector.

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• Participants between 12 and 35 years of age, inclusive, at the time of consent/assent, and able to provide written consent/assent, if applicable.
• Diagnosis of β-thalassemia major and a history of at least 100 mL/kg/year of pRBCs or ≥8 transfusions of pRBCs per year for the prior 2 years.
• Eligible for allogeneic bone marrow transplant.
• Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.

Exclusion Criteria

• Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1 and HIV 2).
• A white blood cell (WBC) count <3 × 10^9/L, and / or platelet count <100 × 10^9/L if not due to hypersplenism.
• Uncorrected bleeding disorder.
• Any prior or current malignancy or myeloproliferative or immunodeficiency disorder.
• Immediate family member with a known or suspected Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome and familial adenomatous polyposis).
• Receipt of an allogeneic transplant.
• Advanced liver disease, including persistent aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin value >3 × the upper limit of normal, liver biopsy demonstrating cirrhosis, extensive bridging fibrosis, or active hepatitis.
• Kidney disease with a calculated creatinine clearance <30% normal value.
• Uncontrolled seizure disorder.
• Diffusion capacity of carbon monoxide (DLco) <50% of predicted (corrected for hemoglobin).
• A cardiac T2* <10 ms by magnetic resonance imaging (MRI).
• Any other evidence of severe iron overload that, in the Investigator's opinion, warrants exclusion.
• Clinically significant pulmonary hypertension, as defined by the requirement for ongoing pharmacologic treatment or the consistent or intermittent use of supplemental home oxygen.
• Participation in another clinical study with an investigational drug within 30 days of Screening.
• Any prior or current malignancy or myeloproliferative disorder.
• Prior receipt of gene therapy.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genetix Biotherapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mohammed Asmal, MD

Role: STUDY_DIRECTOR

Genetix Biotherapeutics Inc.

Locations

Los Angeles, California, United States

Oakland, California, United States

Chicago, Illinois, United States

Philadelphia, Pennsylvania, United States

Sydney, , Australia

Bangkok, , Thailand

Countries

United States; Australia; Thailand

References

Thompson AA, Walters MC, Kwiatkowski J, Rasko JEJ, Ribeil JA, Hongeng S, Magrin E, Schiller GJ, Payen E, Semeraro M, Moshous D, Lefrere F, Puy H, Bourget P, Magnani A, Caccavelli L, Diana JS, Suarez F, Monpoux F, Brousse V, Poirot C, Brouzes C, Meritet JF, Pondarre C, Beuzard Y, Chretien S, Lefebvre T, Teachey DT, Anurathapan U, Ho PJ, von Kalle C, Kletzel M, Vichinsky E, Soni S, Veres G, Negre O, Ross RW, Davidson D, Petrusich A, Sandler L, Asmal M, Hermine O, De Montalembert M, Hacein-Bey-Abina S, Blanche S, Leboulch P, Cavazzana M. Gene Therapy in Patients with Transfusion-Dependent beta-Thalassemia. N Engl J Med. 2018 Apr 19;378(16):1479-1493. doi: 10.1056/NEJMoa1705342.

Reference Type: DERIVED

PMID: 29669226 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

HGB-204

Identifier Type: -

Identifier Source: org_study_id