A Study Evaluating the Safety and Efficacy of Lovo-cel in Severe Sickle Cell Disease

NCT02140554 | Completed Phase 1 Results DMC

• 1 other identifier: HGB-206
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 11

Brief Summary

This is a non-randomized, open label, multi-site, single dose, Phase 1/2 study in approximately 50 adults and adolescents with severe SCD. The study will evaluate hematopoietic stem cell and progenitor stem cell (collectively referred to as hematopoietic stem and progenitor cells or HSPCs) transplantation using lovo-cel.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Percentage of Group C Participants Who Achieved Complete Resolution of Vaso-occlusive Events (VOE-CR)

  VOE-CR was defined as complete resolution of adjudicated VOEs between 6 months and 18 months post lovo-cel infusion. All reported VOEs were also adjudicated by an independent Event Adjudication Committee for purposes of endpoint analysis. VOEs were determined by adjudication committee after referring to protocol VOE. The committee was responsible for VOE assessment and determining whether an event met criteria for a VOE for all reported events.

  From 6 months to 18 months post lovo-cel infusion

Secondary Outcomes (41)

• Percentage of Group C Participants With Complete Resolution of Severe VOEs (sVOE-CR)

  From 6 months to 18 months post lovo-cel infusion

• Percentage of Group C Participants Who Achieved Globin Response

  From at least 60 days after last pRBC transfusion up to Month 24 post lovo-cel infusion

• Percentage of Group C Participants Who Meet the Definition of Globin Response at Month 24

  From first date of Globin Response to Month 24 post lovo-cel infusion

• Duration of Globin Response in Group C Participants

  From first date of Globin Response to Month 24 post lovo-cel infusion

• Change From Baseline in the Annualized Number of VOEs in Group C Participants

  From Baseline up to 24 months post lovo-cel infusion

Study Arms (3)

Group A

EXPERIMENTAL

Participants who had rescue cells that were collected by bone marrow harvest method and had received treatment with lovo-cel which consists of autologous CD34+ hematopoietic stem cells (HSCs) and progenitor stem cells (PSCs) (collectively referred to as hematopoietic stem and progenitor cells or HSPCs) collected from participants with sickle cell disease (SCD) by bone marrow harvest transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene (the original drug product manufacturing process for this study).

Genetic: lovo-cel

Group B

EXPERIMENTAL

Group B1 participant had rescue cells and drug product cells that were collected by bone marrow harvest method and drug product was manufactured with autologous CD34+ HSPCs collected by bone marrow harvest transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene. This participant's drug product was produced in 2 lots each using two different manufacturing processes (the original drug product manufacturing process and a refined drug product manufacturing process). Group B2 Plerixafor mobilization and apheresis were used for collection of rescue cells and exploratory manufacturing development. A single Group B2 participant received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by bone marrow harvest transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene (using only the refined drug product manufacturing process). Note: Groups B1 and B2 are combined as "Group B" for results reporting purposes.

Genetic: lovo-cel

Group C

EXPERIMENTAL

Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.

Genetic: lovo-cel

Interventions

lovo-cel GENETIC

lovo-cel is administered by IV infusion following myeloablative conditioning with busulfan.

Also known as: lovotibeglogene autotemcel, bb1111, LentiGlobin BB305 Drug Product for SCD, autologous CD34+ cell-enriched population with SCD that contains HSCs and PSCs transduced with BB305 lentiviral vector encoding the βA-T87Q-globin gene, suspended in cryopreservation solution.

Group A; Group B; Group C

Eligibility Criteria

• Age: 12 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Be ≥12 and ≤50 of age at time of consent.
• Diagnosis of sickle cell disease (SCD), with either βS/βS or βS/β0 or βS/β+ genotype.
• Have severe SCD. i.e., in the setting of appropriate supportive care measures for SCD (e.g., pain management plan), have experienced at least 4 severe VOEs in the 24 months prior to informed consent.
• For the purposes of this study, a severe VOE is defined as an event with no medically determined cause other than a vaso-occlusion, requiring a ≥ 24-hour hospital or Emergency Room (ER) observation unit visit or at least 2 visits to a day unit or ER over 72 hours with both visits requiring intravenous treatment. Exception: priapism does not require hospital admission but does require a medical facility visit; 4 priapism episodes that require a visit to a medical facility (without inpatient admission) are sufficient to meet criterion.
• Severe VOEs include:
• an episode of acute pain with no medically determined cause other than a VOE
• Acute chest syndrome (ACS), defined by an acute event with pneumonia-like symptoms (e.g., chest pain, fever \[\> 38.5°C\], tachypnea, wheezing or cough, or findings upon lung auscultation) and the presence of a new pulmonary infiltrate consistent with ACS and requiring oxygen treatment and/or blood transfusion.
• Acute hepatic sequestration, defined by a sudden increase in liver size associated with pain in the right upper quadrant, abnormal results of liver-function test not due to biliary tract disease, and reduction in Hb concentration by at least 2 g/dL below the baseline value
• Acute splenic sequestration, defined as sudden enlargement of the spleen and reduction in Hb concentration by at least 2 g/dL below the baseline value.
• Acute priapism: defined as a sustained, unwanted painful erection lasting more than 2 hours and requiring care at a medical facility (with or without hospitalization)
• Karnofsky performance status of ≥ 60 (≥16 years of age) or a Lansky performance status of ≥60 (\<16 years of age).
• Have either experienced hydroxyurea (HU) failure at any point in the past or must have intolerance to HU (defined as patient being unable to continue to take HU per PI judgement).
• Have been treated and followed for at least the past 24 months prior to Informed Consent in medical center(s) that maintained detailed records on SCD history.

You may not qualify if:

• Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 and HIV-2), hepatitis B virus (HBV), or hepatitis C (HCV).
• Clinically significant and active bacterial, viral, fungal, or parasitic infection.
• Inadequate bone marrow function, as defined by an absolute neutrophil count of \< 1000/µL (\< 500/µL for subjects on HU treatment) or a platelet count \< 100,000/µL.
• Any history of severe cerebral vasculopathy: defined by overt or hemorrhagic stroke; abnormal transcranial Doppler \[≥200 cm/sec\] needing chronic transfusion; or occlusion or stenosis in the polygon of Willis; or presence of Moyamoya disease. Subjects with radiologic evidence of silent infarction in the absence of any of the above criteria would still be eligible
• Baseline oxygen saturation \< 90% without supplemental oxygen (excluding periods of SCD crisis, severe anemia or infection).
• Baseline carbon monoxide diffusing capacity (DLCO) \< 50% (corrected for Hb) in the absence of infection. If DLco cannot be assessed due to age or cognition-related restrictions, there must be a normal respiratory exam, chest radiograph without pulmonary infiltrates, and oxygen saturation by pulse oximetry ≥ 90% on room air.
• Baseline left ventricular ejection fraction (LVEF) \< 45% measured by cardiac echography.
• Clinically significant pulmonary hypertension at baseline, as defined by the requirement for ongoing pharmacologic treatment or the consistent or intermittent use of supplemental home oxygen.
• Baseline estimated glomerular filtration rate (eGFR) \< 70 mL/min/1.73 m2, as determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (see http://www.kidney.org/professionals/kdoqi/gfr\_calculator.cfm).
• Advanced liver disease, defined as:
• Persistent aspartate transaminase, alanine transaminase, or direct bilirubin value \>3× the upper limit of normal (ULN), or
• Baseline prothrombin time or partial thromboplastin time \>1.5× ULN, suspected of arising from liver disease, or
• Magnetic Resonance Imaging (MRI) of the liver demonstrating clear evidence of cirrhosis, or
• Contraindication to anesthesia.
• Any contraindications to the use of plerixafor during the mobilization of hematopoietic stem cells and any contraindications to the use of busulfan and any other medicinal products required during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.

Sponsors & Collaborators

• Genetix Biotherapeutics Inc.: lead

Study Sites (11)

Unknown Facility

Birmingham, Alabama, United States

Location

Unknown Facility

Oakland, California, United States

Location

Unknown Facility

Atlanta, Georgia, 30322, United States

Location

Unknown Facility

Chicago, Illinois, United States

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Unknown Facility

Bethesda, Maryland, United States

Location

Unknown Facility

Hackensack, New Jersey, United States

Location

Unknown Facility

New Hyde Park, New York, United States

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Unknown Facility

New York, New York, United States

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Unknown Facility

Chapel Hill, North Carolina, United States

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Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Charleston, South Carolina, United States

Location

Related Publications (5)

• Kanter J, Thompson AA, Pierciey FJ Jr, Hsieh M, Uchida N, Leboulch P, Schmidt M, Bonner M, Guo R, Miller A, Ribeil JA, Davidson D, Asmal M, Walters MC, Tisdale JF. Lovo-cel gene therapy for sickle cell disease: Treatment process evolution and outcomes in the initial groups of the HGB-206 study. Am J Hematol. 2023 Jan;98(1):11-22. doi: 10.1002/ajh.26741. Epub 2022 Oct 10.

  PMID: 36161320 DERIVED

• Del Pozo Martin Y. 2021 ASH annual meeting. Lancet Haematol. 2022 Feb;9(2):e92-e93. doi: 10.1016/S2352-3026(21)00384-7. Epub 2021 Dec 16. No abstract available.

  PMID: 34922648 DERIVED

• Kanter J, Walters MC, Krishnamurti L, Mapara MY, Kwiatkowski JL, Rifkin-Zenenberg S, Aygun B, Kasow KA, Pierciey FJ Jr, Bonner M, Miller A, Zhang X, Lynch J, Kim D, Ribeil JA, Asmal M, Goyal S, Thompson AA, Tisdale JF. Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease. N Engl J Med. 2022 Feb 17;386(7):617-628. doi: 10.1056/NEJMoa2117175. Epub 2021 Dec 12.

  PMID: 34898139 DERIVED

• Jones RJ, DeBaun MR. Leukemia after gene therapy for sickle cell disease: insertional mutagenesis, busulfan, both, or neither. Blood. 2021 Sep 16;138(11):942-947. doi: 10.1182/blood.2021011488.

  PMID: 34115136 DERIVED

• Del Pozo Martin Y. 47th Annual Meeting of the EBMT. Lancet Haematol. 2021 May;8(5):e317-e318. doi: 10.1016/S2352-3026(21)00104-6. Epub 2021 Mar 31. No abstract available.

  PMID: 33811823 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

lyfgenia; Excipients

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pharmaceutical Vehicles; Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Results Point of Contact

• Title: Study Medical Director
• Organization: bluebird bio, Inc

medinfo@bluebirdbio.com

339-499-9300

Study Officials

• Anjulika Chawla, MD, FAAP

  bluebird bio, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2014
• First Posted: May 16, 2014
• Study Start: February 2, 2015
• Primary Completion: July 31, 2023
• Study Completion: January 30, 2024
• Last Updated: March 14, 2025
• Results First Posted: October 8, 2024

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

US (11)