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NCT 02140554
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A Study Evaluating the Safety and Efficacy of the bb1111 in Severe Sickle Cell Disease |
Phase 1/2, open-label, n=50
Gene addition, modified β: β-AT87Q |
Active, not recruiting;
Estimated completion date: 3/2023 |
SCD with either βS/βS or βS/β0 or (βS/β+ genotype
Aged 12 to 50 years old
All genders
United States |
Proportion of subjects achieving complete resolution of severe vaso-occlusive events, between 6 months and 18 months after drug product infusion |
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 Karnofsky performance status of ≥ 60 (≥16 years of age) or a Lansky performance status of ≥60 (<16 years of age) Have either experienced HU failure at any point in the past or must have intolerance to HU
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NCT 02151526
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A Study Evaluating the Safety and Efficacy of LentiGlobin BB305 Drug Product in β-Thalassemia Major (Also Referred to as Transfusion-dependent β-Thalassemia [TDT]) and Sickle Cell Disease |
Phase 1/2, open-label, n=7
Gene addition, modified β: β-AT87Q |
Completed; Completion date: 2/16/2019 |
Severe SCD or transfusion dependent β-thalassemia major, regardless of the genotype with the diagnosis confirmed by Hb studies. (Transfusion dependence defined as requiring at least 100 mL/kg/year of packed red blood cells (pRBCs).)
Aged 5 to 35 year old
All genders
France |
Number of treated participants with successful neutrophil and platelet engraftment Time to successful neutrophil and platelet engraftment Incidence of transplant related mortality Number of participants with OS events Percentage of participants with vector-derived RCL Number of treated participants with > 30% contribution of an individual clone as per integration site analysis (ISA) Number of participants with AEs and SAEs
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Eligible for allogeneic HSCT based on institutional medical guidelines, but without a matched related donor Have failed to achieve adequate clinical benefit following HU treatment with sufficient dosage, for at least 4 months unless this treatment was not indicated or not well tolerated Have 1 or more of the following poor prognostic risk factors: Recurrent VOC (at least 2 episodes in the preceding year or in the year prior to start of a regular transfusion program). Presence of any significant cerebral abnormality on MRI Stroke without any severe cognitive disability Osteonecrosis of 2 or more joints Anti-erythrocyte alloimmunization (>2 antibodies) Presence of sickle cell cardiomyopathy documented by Doppler echocardiography ACS (at least 2 episodes) defined by an acute event with pneumonia-like symptoms and the presence of a new pulmonary infiltrate
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NCT 02186418
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Gene Transfer for Patients with Sickle Cell Disease |
Phase 1/2, open-label, n=10 Gene addition, modified γ: ARU-1801 |
Recruiting; Estimated completion date: 6/2035 |
Sickle cell disease (SCD) Aged 18 to 45 years old
All genders
United States, Canada, Jamaica |
Incidence of Grade 3 allergic reaction Incidence of Grade 4 infection Incidence of Grade 4 neutropenia Incidence of Grade 3 or 4 organ toxicity Incidence of AEs Incidence of SAEs Incidence of death due to study procedures Incidence of hematological malignancy Incidence of hematological malignancy due to vector insertion Incidence of hematological cancer Time to neutrophil recovery Time to platelet recovery ≥8x106kg viable CD34+ cells (Number of subjects with a total number of CD34+ cells recovered from all collections combined (mobilized peripheral blood and bone marrow) of at least ≥8x106kg viable CD34+ cells) >4x106 CD34+ cells/kg body weight transduced (Proportion of subjects for which a minimum of 4x105 CD34+ cells/kg body weight from all collections combined have been successfully transduced) Bone marrow aspirates with ≥1% gene-marked cells (Number of subjects with bone marrow aspirates at 1-year post-infusion with ≥1% gene-marked cells)
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Has severe SCD, defined as one or more of the following: Minimum of two episodes of clinically diagnosed ACS requiring hospital admission, or one life threatening episode of ACS requiring ICU admission for exchange transfusion and/or intubation, or frequent ACS episodes which necessitate treatment with chronic transfusion therapy Frequent painful VOEs which significantly interfere with normal life activities, defined as a history of 2 or more severe acute sickle pain events per year requiring additional treatment at a medical facility outside of home pain management over the preceding 2-year period prior to study enrollment, or that necessitate chronic transfusion therapy Subjects on chronic transfusion therapy for severe disease symptoms other than those listed above, and which interfere with normal life activities Has failed HU therapy, was unable to tolerate HU therapy, or has actively made the choice to not take the recommended daily HU advised for severe disease Has adequate functional status and organ function as determined at Screening
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NCT 02247843
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Stem Cell Gene Therapy for Sickle Cell Disease |
Phase 1/2, open-label, n=6
Gene addition, modified β: β-AS3-FB |
Recruiting; Estimated completion date: 8/2022 |
SCD documented by genetic analysis (SIS, S/β-thalassemia-zero)
Aged 18 years or older
All genders
University of California, Los Angeles (UCLA), United States |
Clinical toxicity: Absence of grade 3-4 SAEs Absence of RCL Absence of monoclonal expansion or leukoproliferative disorder from vector insertional effects Event-free survival Absence of humoral immune response to novel epitopes of βAS3-globin protein
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Inadequate clinical response to HU, defined as any one of the following outcomes, while on HU for at least 3 months: 2 or more acute sickle pain crises requiring hospitalization no rise in Hb >1.5 gm/dl from pre-HU baseline or requires transfusion to maintain Hb > 6.0 gm/dL Has an episode of ACS defined as development of a new pulmonary alveolar consolidation involving at least one complete lung segment associated with acute symptoms and the ACS event occurred despite adequate supportive care measures Medical decision for other therapy (e.g., chronic transfusion program), or subject refusal to take HU. The patient must be off HU for at least 30 days (+/− 5 days) before PBSC collection. Must have one or more of the following clinical complications demonstrating disease severity: Clinically significant neurologic event: stroke or any central nervous system deficit lasting >24 hours. Abnormal head CT or brain MRI demonstrating previous stroke Administration of regular RBC transfusions for equal or longer than 1 year to prevent vasoocclusive crises or other sickle cell disease complications or to maintain Hb >6. Pulmonary arterial hypertension with tricuspid regurgitant jet velocity > 2.5 m/sec within 1 year prior to enrollment At least one episode of acute chest syndrome that required hospitalization, within the 2 years prior to enrollment At least 2 acute sickle pain crises requiring hospitalization within the 2 years prior to enrollment Severe osteonecrosis History of acute dactylitis during childhood Recurrent priapism (2 or more episodes) Karnofsky performance score ≥60%
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NCT 02633943
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Long term Follow-up of Subjects with Hemoglobinopathies Treated with Ex Vivo Gene Therapy |
Follow-up, observational
n=94
β-AT87Q |
Enrolling by invitation;
Estimated completion date: 3/1/2031 |
β-thalassemias and SCD
Up to the age of 50; all genders
United States, Australia, France, Italy, Thailand |
Overall survival of subjects with β-thalassemias and SCD treated with gene therapy drug product in a bluebird bio-sponsored clinical study All AEs related to drug product All SAEs Monitoring for persistence of vector sequences by polymerase chain reaction to determine VCN Monitoring of βA-T87Q-globin Assessment of transfusions required (mL of packed red blood cells/kg/year) in subjects with β-thalassemia Assessment of iron content in the liver and heart by cardiac MRI and blood draws in subjects with β-thalassemia Frequency of AEs from subjects with severe sickle cell disease including ACS, severe VOC, and stroke or ischemic attacks
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NCT 03282656
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Gene Transfer for Sickle Cell Disease |
Phase 1, open-label, n=15
Gene silencing, BCH-BB694 lentiviral vector (short hairpin RNA targeting BCL11a) |
Active, not recruiting;
Estimated completion date: 4/13/2024 |
SCD with genotype HbSS, HbS/0 thalassemia, HbSD, or HbSO
Age 3 to 40 years old
All genders Boston Children’s Hospital, United States |
Rescue of hematopoiesis after conditioning |
Severe symptomatic SCD, defined by the presence of one or more of the following clinical complications: Minimum of two episodes of ACS in the 2 years before study entry History of three or more episodes of severe pain events requiring a visit to a medical facility and treatment with parenteral opioids in the 2 years before study entry Recurrent priapism (> 2 episodes) in the 2 years before study entry Red cell alloimmunization (>2 antibodies) during long-term transfusion therapy. Receiving, or indicated to receive chronic transfusions for primary or secondary stroke prophylaxis -
Failure of HU therapy due to lack of clinical improvement or inability to tolerate due to side effects
WBC count within the range of 3.0 - 20.0 x 109/L Hemoglobin within the range of 5 - 11 g/dL
Platelet count within the range of 100 - 600 x 109 /L PT and PTT within normal limits, unless prolonged due to anticoagulation requirement.
Adequate organ function and performance status: Performance status ≥70% (Lansky play for age <16 years, Karnofsky for age ≥16 years) LVEF >40% or shortening fraction >25% Direct bilirubin ≤ 2.0 mg/dL Serum creatinine ≤ 1.5 times the upper limit of normal for age, and creatinine clearance or GFR ≥ 70 mL/min/1.73 m2 For ages > 7 years, DLCO (corrected for hemoglobin), FEV1, FVC >50% of predicted; if age < 7 years, then oxygen saturation >92% on room air
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NCT 03653247
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A Study to Assess the Safety, Tolerability, and Efficacy of BIVV003 for Autologous Hematopoietic Stem Cell Transplantation in Patients with Severe Sickle Cell Disease |
Phase 1/2, open-label, n=8
Zn finger editing of BCL11a:BIVV003 |
Recruiting;
Estimated completion date: 11/2023 |
SCD (HbSS or HbSβ0 genotype)
Age 18 to 40 years old
All genders
UCSF Benioff Children’s Hospital; University of California Davis Comprehensive Cancer Center; Children’s Healthcare of Atlanta; Karmanos Cancer Institute, United States |
Percentage of participants who are alive at post-transplantation Day 100 Percentage of participants who are alive at post-transplantation Week 52 Percentage of participants who are alive at post-transplantation Week 104 Percentage of participants with successful engraftment Number of participants with AEs Number of participants with SAEs
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Severe SCD, defined as having 1 or more of the following manifestations: Clinically significant neurologic event (e.g., stroke) or any neurological deficit lasting more than 24 hours History of 2 or more episodes or ACS in 2 years prior to informed consent (despite adequate supportive therapies such as asthma therapy) Six or more pain crises per year in 2 years prior to informed consent (requiring IV pain management in the outpatient or inpatient hospital setting) History of 2 or more cases of priapism with participant seeking medical care in the 2-years prior to informed consent Regular RBC transfusion therapy in the year prior to informed consent (having received 8 or more transfusions to prevent vaso-occlusive clinical complications); and Echocardiographic finding of TRJ velocity of greater than or equal to 2.5 m/s Clinically stable to undergo stem cell mobilization and myeloablative HSCT Adequate physiological function, defined as the following: Karnofsky/Lansky Performance of greater than or equal to 60; Acceptable cardiac function as defined in protocol; Acceptable pulmonary function as defined in protocol; Acceptable renal function as defined in protocol; and Acceptable hepatic function as defined in protocol Completion of age-appropriate cancer screening Willingness to receive blood transfusions Willingness to discontinue HU at least 30 days prior to stem cell mobilization through Day 100 post-transplantation
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NCT 03745287
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A Safety and Efficacy Study Evaluating CTX001 in Subjects with Severe Sickle Cell Disease |
Phase 1/2, open-label, n=45
CRISPR editing of BCL11a:CTX001 |
Recruiting;
Estimated completion date: 5/2022 |
Severe SCD (by genotype)
Age 18 to 35 years old
United States, Belgium, Canada, Germany, Italy |
Proportion of subjects with HbF ≥20%, sustained for at least 3 months at the time of analysis, starting 6 months after CTX001 infusion Proportion of subjects with engraftment (absolute neutrophil count [ANC] ≥500/-μL for three consecutive days) Time to engraftment Frequency and severity of collected AEs Incidence of TRM within 100 days after CTX001 infusion Incidence of TRM within 1 year after CTX001 infusion All-cause mortality
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NCT 03964792
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Safety and Efficacy of Gene Therapy of the Sickle Cell Disease by Transplantation of an Autologous CD34+ Enriched Cell Fraction That Contains CD34+ Cells T ransduced ex Vivo with the GLOBE1 Lentiviral Vector Expressing the βAS3 Globin Gene in Patients with Sickle Cell Disease (DREPAGLOBE) |
Phase 1, open-label, n=10
Gene addition, modified β: β-AS3 |
Recruiting Estimated completion date: 11/12/2024 |
HbSS or S-β zero thalassemia
Age 5 to 35 years old;
All genders
Department of Biotherapy Necker-Enfants Malades Hospital, France |
Incidence of transplant related mortality Incidence of the need for rescue autologous bone marrow transplant Frequency and severity of AEs post-transplant Incidence of vector-derived RCL Incidence of clinically detectable malignancy and/or abnormal clonal dominance assessed as related to study treatment
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Clinical history or ongoing evidence of severe sickle cell anemia with one OR more of the following clinical complications demonstrating disease severity: At least 3 vaso-occlusive crises requiring hospitalization, under hydroxyurea or transfusion, within 2 years prior to enrollment One severe ACS hospitalized in intensive care unit At least 2 episodes of ACS within the prior 3 years), including one under HU. Acute priapism (at least 2 episodes > 3h in the preceding year or in the year prior to the start of a regular transfusion program), OR stuttering priapism ≥ 1 by week under sickle cell treatment (HU, transfusion or phlebotomy). Cerebral vasculopathy confirmed by MRA without Moyamoya Presence of sickle cell cardiomyopathy documented by Doppler echocardiography (LVEF <55% AND tricuspid regurgitation velocity >2.5m/s on cardiac echocardiograph), Tricuspid regurgitation velocity >2.8m/s on cardiac echocardiograph without pulmonary hypertension confirmed by right heart catheterization (mPAP<25mmHg) Failed HU therapy; were unable to tolerate HU therapy, or, if 18 years of age or older, have actively made the choice to not take the recommended daily HU regimen. Inadequate clinical response to HU, defined as any one of the following outcomes, while on HU for at least 3 months: 2 or more acute sickle pain crises requiring hospitalization, no rise in Hb >1.5 gm/dL from pre-HU baseline or requires transfusion to maintain Hb > 6.0 gm/dL, had an episode of ACS despite adequate supportive care measures Karnofsky/Lansky performance score ≥ 60%
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NCT 04091737
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CSL200 Gene Therapy in Adults with Severe Sickle Cell Disease |
Phase 1, open-label, n=3
Gene addition, modified gamma with siRNA for selection: Gamma globin G16D-RNA734 |
Active, not recruiting;
Estimated completion date: 7/2021 |
SCD with homozygous HbSS or an HbSβ thalassemia variant (ie, HbSβ0 thalassemia or HbSβ+ thalassemia)
Age 18 to 45 years old;
All genders
City of Hope Medical Center, United States |
Number of AEs, SAEs, and AESIs associated with the administration of CSL200 Number of subjects experiencing AEs, SAEs, and AESIs associated with the administration of CSL200 Number of AEs, SAEs, and AESIs associated with the collection of CD34+ HSPCs by apheresis after mobilization with plerixafor Number of subjects experiencing AEs, SAEs, and AESIs associated with the collection of CD34+ HSPCs by apheresis after mobilization with plerixafor Number of AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan Number of subjects experiencing AEs, SAEs, and AESIs associated with reduced intensity conditioning with melphalan
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HbF ≤ 15%. Severe sickle cell disease symptomatology, defined as any one or more of the following: ≥ 2 episodes of ACS in the last 2 years ≥ 3 episodes of severe pain events requiring a visit to a medical facility and treatment with opioids in the last 2 years > 2 episodes of recurrent priapism in the last 2 years Red cell alloimmunization (> 2 antibodies) during long-term transfusion therapy (lifetime history) Chronic transfusions for primary or secondary prophylaxis (lifetime history). Trans-thoracic echocardiograph evidence of tricuspid valve regurgitant jet velocity ≥ 2.7 m/s (lifetime history) Clinically significant neurologic event (eg, ischemic stroke) or any neurological deficit lasting > 24 hours
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NCT 04208529
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A Long-term Follow-up Study in Subjects Who Received CTX001 |
Follow-up, observational
n=90
CTX001 |
Enrolling by invitation;
Estimated completion date: 9/1/2039 |
Subjects must have received CTX001 infusion
Age 18 years and older
All genders United States, Germany, Italy |
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NCT 04293185
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A Study Evaluating Gene Therapy with BB305 Lentiviral Vector in Sickle Cell Disease |
Phase 3, open-label, n=35
Gene addition, modified β: β-AT87Q |
Recruiting;
Estimated completion date: 11/2023 |
SCD βS/βS, βS/β0 or βS/β+)
Age 2 to 50 years old
All genders
University of Minnesota, Baylor College of Medicine; Texas Children’s Hospital, United States |
Proportion of subjects meeting Globin Response criteria |
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) Have severe manifestations of SCD. i.e., in the setting of appropriate supportive care measures, have experienced at least 4 severe VOEs in the 24 months prior to informed consent as defined below Have either experienced HU failure at any point in the past or must have intolerance to HU
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NCT 04443907
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Study of Safety and Efficacy of Genome-edited Hematopoietic Stem and Progenitor Cells in Sickle Cell Disease (SCD) |
Phase 1/2, open-label, n=20
Gene editing of BCL11a:OTQ923 and/or HIX763 |
Recruiting;
Estimated completion 11/20/2023 |
SCD (HbSS, HbSC, HbS/β0-thalassemia or others)
Age 2 to 40 years old
All genders
Memphis, Tennessee, United States |
Number of adverse events in 2 years (safety and tolerability of genome-edited HSC in subjects with sickle cell disease, time to engraftment, and HbF expression) Number of participants with fetal hemoglobin expression (Quantity - HbF expression after HSCT)
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Performance status <70% (karnofsky for subjects >16 years of age and Lansky for subjects <16 years of age) At least one of the following indicators of disease severity (VOE, ACS, recurrent priapism, prior stroke, receive chronic transfusions, red cell alloimmunization) Subjects, who have failed, tolerated or refused HU therapy
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NCT 04628585
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Long-term Follow-up of Subjects with Sickle Cell Disease Treated with Ex Vivo Gene Therapy |
Follow-up, observational
n=85
β-AT87Q |
Enrolling by invitation;
Estimated completion date: 5/2037 |
SCD treated with ex vivo gene therapy product in bluebird bio-sponsored clinical studies
Age 2 to 53 years old
All genders
Columbia University Medical Center, New York;
Medical University of South Carolina, South Carolina; Hospital Necker, France |
Non-transfused total Hb over 15 years post-drug product infusion |
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