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Sickle Cell DiseasePhase 3NCT04293185

A Study Evaluating Gene Therapy With BB305 Lentiviral Vector in Sickle Cell Disease

A Phase 3 study testing bb1111 in people with Sickle Cell Disease, run by Genetix Biotherapeutics Inc. at 9 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a non-randomized, open-label, multi-site, single-dose, Phase 3 study in approximately 35 adults and pediatric subjects ≥2 and ≤50 years of age with sickle cell disease (SCD). Read more about this study

Who is it for?
Ages 2 to 50 years
Conditions the study is for
Sickle Cell Disease
What is being tested?
bb1111
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
9 sitesUnited States
Study dates
14 Feb 2020to Nov 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 50 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Have a diagnosis of SCD, with either βS/βS, βS/β0, or βS/β+ genotype.
  • Be ≥2 and ≤50 years of age at time of consent.
  • Weigh a minimum of 6 kg.
  • Have a Karnofsky performance status of ≥60 (≥16 years of age) or a Lansky performance status of ≥60 (<16 years of age).
  • Be treated and followed for at least the past 24 months prior to Informed Consent in medical center(s) that maintained detailed records on sickle cell disease history.
  • In the setting of appropriate supportive care measures (e.g., pain management plan), have experienced at least 4 protocol-defined VOEs in the 24 months prior to informed consent.
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  • Have either experienced HU failure at any point in the past or must have intolerance to HU (intolerance is defined as the patient being unable to continue to take HU per PI judgment).
  • Female and male subjects of childbearing potential agree to use 1 method of highly effective contraception from Screening to at least 6 months after drug product infusion.
  • Provision of written informed consent for this study by subject, or as applicable, subject's parent(s)/legal guardian(s).

Who cannot join

  • Subjects for whom allogeneic hematopoietic stem cell transplantation (allo-HSCT) is medically appropriate per PI judgment and a willing, human leukocyte antigen (HLA)-matched related hematopoietic stem cell donor is available.
  • Severe cerebral vasculopathy, defined by any history of overt ischemic or hemorrhagic stroke, a history of abnormal transcranial Doppler (TCD) or TCD imaging (TCDI) for subjects ≤ 16 years of age (e.g. TCD velocity >200 cm/sec) requiring ongoing chronic transfusions, a Screening TCD or TCDI velocity > 200 cm/sec (central read), a Screening MRA showing > 50% stenosis or occlusion in the circle of Willis (central read), or a Screening MRA showing the presence of Moyamoya (central read).
  • Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2), hepatitis B, hepatitis C, human T-lymphotropic virus-1 (HTLV-1), active syphilis.
  • Clinically significant, active bacterial, viral, fungal, or parasitic infection
  • Advanced liver disease, such as
  • clear evidence of liver cirrhosis, active hepatitis or significant fibrosis (based on MRI or liver biopsy)
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  • liver iron concentration ≥15 mg/g unless liver biopsy shows no evidence of cirrhosis, active hepatitis or significant fibrosis
  • Inadequate bone marrow function, as defined by an absolute neutrophil count of <1×10^9/L (<0.5×10^9/L for subjects on hydroxyurea treatment) or a platelet count <100×10^9/L.
  • 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.
  • Patients needing therapeutic anticoagulation treatment during the period of conditioning through platelet engraftment
  • Unable to receive pRBC transfusion.
  • Prior receipt of an allogeneic transplant.
  • Prior receipt of gene therapy.
  • Any prior or current malignancy or immunodeficiency disorder, except previously treated, non-life threatening, cured tumors such as squamous cell carcinoma of the skin.
  • Immediate family member with a known or suspected Familial Cancer Syndrome.
  • Female subject is breastfeeding, pregnant or will attempt to become pregnant from Screening to at least 6 months after drug product infusion.
  • Any other condition that would render the subject ineligible for HSCT.
  • Participation in another clinical study with an investigational drug within 30 days of screening.
  • Presence of a chromosomal abnormality or genetic mutation that may put the subject at an increased risk of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) per Investigator's judgment.
  • Presence of genetic mutations that result in the inactivation of 2 or more α-globin genes

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • University of Alabama

    Birmingham, Alabama, 35233

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Duke University

    Durham, North Carolina, 27705

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Baylor College of Medicine/Texas Children's Hospital

    Houston, Texas, 77030

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Virginia Commonwealth University (VCU)

    Richmond, Virginia, 23219

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • Children's National Hospital

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: A Phase 3 Study Evaluating Gene Therapy by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With the BB305 Lentiviral Vector in Subjects With Sickle Cell Disease

This is a non-randomized, open-label, multi-site, single-dose, Phase 3 study in approximately 35 adults and pediatric subjects ≥2 and ≤50 years of age with sickle cell disease (SCD). The study will evaluate hematopoietic stem cell (HSC) transplantation (HSCT) using bb1111 (also known as LentiGlobin BB305 Drug Product for SCD).

Being tested
bb1111
Medical subject headings
Anemia, Sickle Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bb1111Genetic

    Also called lovotibeglogene autotemcel, lovo-cel, LentiGlobin BB305 Drug Product for SCD, autologous CD34+ cell-enriched population from patients with SCD that contains HSCs transduced with BB305 LVV encoding the βA-T87Q-globin gene, suspended in cryopreservation solution

    Drug Product is administered by IV infusion following myeloablative conditioning with busulfan.

Study groups in NCT04293185
Study groupRoleWhat they receive
bb1111ExperimentalSubjects will receive treatment with a single dose of Drug Product manufactured with autologous CD34+ hematopoietic stem cells collected by plerixafor mobilization and apheresis, transduced with BB305 lentiviral vector (LVV) encoding the human beta-A-T87Q globin gene. Plerixafor mobilization and apheresis will also be used for collection of rescue cells.
Receives: Genetic: bb1111

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. VOE-CR

    Proportion of subjects achieving complete resolution of VOEs between 6 months and 18 months after drug product infusion

    Measured: 6-18 months post-transplant

Secondary outcomes (34)

  1. sVOE-CR

    Proportion of subjects achieving complete resolution of severe vaso-occlusive events, between 6 months and 18 months after drug product infusion

    Measured: 6-18 months post-transplant

  2. Proportion of subjects achieving Globin Response

    Globin Response, defined as meeting the following criteria for a continuous period of at least 6 months after drug product infusion:

    1. Weighted average HbAT87Q percentage of non-transfused total Hb* ≥30% AND
    2. Weighted average non-transfused total Hb* increase of ≥3 g/dL compared to baseline total Hb* OR weighted average non-transfused total Hb* ≥10 g/dL
    • non-transfused total Hb is the total g/dL of HbS + HbF + HbA2 + HbAT87Q

    Measured: 6-24 months post-transplant

  3. Change in the annualized number of VOEs in the 24 months after drug product infusion compared to the 24 months prior to Informed Consent

    Measured: 1-24 months post-transplant

  4. Change in the annualized number of severe VOEs in the 24 months after drug product infusion compared to the 24 months prior to Informed Consent.

    Measured: 1-24 months post-transplant

  5. VOE-CR24

    Proportion of subjects achieving complete resolution of VOEs between 6 months and 24 months after drug product infusion

    Measured: 6-24 months post-transplant

  6. sVOE-CR24

    Proportion of subjects achieving complete resolution of severe VOEs between 6 months and 24 months after drug product infusion

    Measured: 6-24 months post-transplant

  7. sVOE-75

    Proportion of subjects achieving at least a 75% reduction in annualized severe VOEs in the 24 months after drug product administration compared to the 24 months prior to Informed Consent.

    Measured: 1-24 months post-transplant

  8. Weighted average non-transfused total Hb

    Measured: Month 6, 12, 18 and 24 post-transplant

  9. Weighted average HbS percentage of non-transfused total Hb

    Measured: Month 6, 12, 18 and 24 post-transplant

  10. Weighted average HbS percentage of non-transfused total Hb ≤70%, ≤60%, ≤50%

    Measured: Month 6, 12, 18 and 24 post-transplant

  11. Weighted average HbAT87Q percentage of non-transfused total Hb

    Measured: Month 6, 12, 18 and 24 post-transplant

  12. Weighted average non-HbS percentage of non-transfused total Hb

    Measured: Month 6, 12, 18 and 24 post-transplant

  13. Average and median of non-transfused total Hb

    Measured: 1-24 months post-transplant

  14. Average and median of HbS percentage of non-transfused total Hb

    Measured: 1-24 months post-transplant

  15. Average and median of HbAT87Q percentage of non-transfused total Hb

    Measured: 1-24 months post-transplant

  16. Average and median of non-HbS percentage of non-transfused total Hb

    Measured: 1-24 months post-transplant

  17. Change from baseline in absolute reticulocyte count

    Measured: 1-24 months post-transplant

  18. Change from baseline in percent reticulocytes

    Measured: 1-24 months post-transplant

  19. Change from baseline in percent erythrocytes

    Measured: 1-24 months post-transplant

  20. Change from baseline in total bilirubin

    Measured: 1-24 months post-transplant

  21. Change from baseline in haptoglobin

    Measured: 1-24 months post-transplant

  22. Change from baseline in lactate dehydrogenase

    Measured: 1-24 months post-transplant

  23. Change from baseline in ferritin

    Measured: 1-24 months post-transplant

  24. Change from baseline in liver iron content

    Measured: 1-24 months post-transplant

  25. Change from baseline in cardiac iron content (if assessed at baseline)

    Measured: 1-24 months post-transplant

  26. Change from baseline in erythropoietin

    Measured: 1-24 months post-transplant

  27. Change from baseline in serum transferrin receptor

    Measured: 1 - 24 months post-transplant

  28. Change from baseline in annualized frequency of packed red blood cell (pRBC) transfusions

    Measured: 6-24 months post-transplant

  29. Change from baseline in annualized volume of pRBC transfusions

    Measured: 6-24 months post-transplant

  30. Change from baseline in TCD velocity at Month 12 and Month 24 (for subjects ≤ 16 years old at Informed Consent)

    Measured: Month 12 and Month 24 post-transplant

  31. Change from baseline in meters walked during the 6-minute walk test

    Measured: 1 - 24 months post-transplant

  32. Change from baseline in annualized number of SCD-related hospital admissions

    Measured: 1 - 24 months post-transplant

  33. Change from baseline in annualized number of total days hospitalized

    Measured: 1 - 24 months post-transplant

  34. Change from baseline in patient-reported quality of life, as measured by PROMIS-57 Version 2.1 for subjects ≥ 18 years of age and PROMIS Pediatric Profile/Parent Proxy Profile 49 Version 2.0 for subjects < 18 years of age

    Measured: 1 - 24 months post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Mar 2020
  2. Study start14 Feb 2020
  3. Primary completionMay 2027 (estimated)
  4. Study completionNov 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04293185
Sponsor's protocol ID
HGB-210
Status last verified
Dec 2024
First submitted
12 Feb 2020
Last updated
10 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Bluebird bio is committed to transparency and appropriately de-identified patient-level datasets and supporting documents may be shared upon completion of study participation and following attainment of applicable marketing approvals associated with this study and consistent with criteria established by bluebird bio and/or industry best practices to maintain the privacy of study participants. For enquiries, please contact us at datasharing@bluebirdbio.com.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing bb1111 in people with Sickle Cell Disease, run by Genetix Biotherapeutics Inc. at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 10 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

VOE-CR (time frame: 6-18 months post-transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04293185.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2024.

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