Clinical trial NCT04208529: A Long-term Follow-up Study in Participants Who Received CTX001
Official title: A Long-term Follow-up Study of Subjects With β-thalassemia or Sickle Cell Disease Treated With Autologous CRISPR-Cas9 Modified Hematopoietic Stem Cells (CTX001)
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Beta-Thalassemia
Thalassemia
Sickle Cell Disease
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Sickle Cell Anemia
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
Collaborators: name: CRISPR Therapeutics
First posted: 2019-12-23
Enrollment: 160
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Long Term Safety Follow-up
Primary purpose: OTHER

Brief summary: This is a multi-site, open- label rollover study to evaluate the long-term safety and efficacy of CTX001 in pediatric and adult participants who received CTX001 in parent studies 111 (NCT03655678) 141 (NCT05356195) or 161 (NCT05477563) (transfusion-dependent β-thalassemia \[TDT\] studies) or Study 121 (NCT03745287) or 151 (NCT05329649), 161(NCT05477563),171 (NCT05951205) (severe sickle cell disease \[SCD\] studies).


Eligibility criteria: Inclusion Criteria:

* Participants (or his or her legally appointed and authorized representative or guardian) must sign and date informed consent form (ICF) and, where applicable, an assent form
* Participants must have received CTX001 infusion in a parent study

Exclusion Criteria:

* There are no exclusion criteria

Primary outcomes:
measure: New malignancies
timeFrame: Signing of informed consent up to 15 years post CTX001 infusion
measure: New or worsening hematologic disorders
timeFrame: Signing of informed consent up to 15 years post CTX001 infusion
measure: All-cause mortality
timeFrame: Signing of informed consent up to 15 years post CTX001 infusion
measure: Serious adverse events (SAEs)
timeFrame: Signing of informed consent up to 15 years post CTX001 infusion
measure: CTX001-related adverse events (AEs)
timeFrame: Signing of informed consent up to 15 years post CTX001 infusion
Secondary outcomes:
measure: TDT and SCD: Total Hemoglobin (Hb) concentration over time
timeFrame: Up to 15 years post CTX001 infusion
measure: TDT and SCD: Fetal Hemoglobin (HbF) concentration over time
timeFrame: Up to 15 years post CTX001 infusion
measure: TDT and SCD: Proportion of alleles with intended genetic modification present in peripheral blood over time
timeFrame: Up to 15 years post CTX001 infusion
measure: TDT and SCD: Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time
timeFrame: Up to 15 years post CTX001 infusion
measure: TDT and SCD: Change in patient-reported outcome (PRO) over time in participants ≥18 years of age assessed using EuroQol quality of life scale (EQ-5D-5L) for participants from study 111,121 and 171 only
timeFrame: Up to 5 years post CTX001 infusion
measure: TDT and SCD: Change in PROs over time in participants ≥18 years of age assessed using functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) questionnaire for participants from study 111, 121, 161 and 171 only
timeFrame: Up to 5 years post CTX001 infusion
measure: TDT and SCD: Change in PROs over time in participants <18 years assessed using EQ-5D-Youth (EQ-5D-Y) from study 111,121,141,151 and 171 only
timeFrame: Up to 5 years post CTX001 infusion
measure: TDT and SCD: Change in PROs over time in participants <18 years assessed using pediatric quality of life inventory (PedsQL) Core
timeFrame: Up to 5 years post CTX001 infusion
measure: TDT: Proportion of participants achieving transfusion independence for at least 12 consecutive months (TI12)
timeFrame: From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
measure: TDT: Proportion of participants achieving transfusion independence for at least 6 consecutive months (TI6)
timeFrame: From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
measure: TDT: Proportion of participants achieving at least 95%, 90%, 85%, 75%, 50% reduction from baseline in annualized transfusions starting 60 days after CTX001 infusion
timeFrame: From Day 60 up to 15 years post-CTX001 infusion
measure: TDT: Duration of transfusion free in participants who have achieved TI12
timeFrame: From 60 days after last RBC transfusion up to 15 years post CTX001 infusion
measure: TDT: Relative reduction from baseline in annualized volume of RBC transfusions
timeFrame: From Day 60 up to 15 years post-CTX001 infusion
measure: TDT: Iron overload as measured by liver iron concentration (LIC), cardiac iron concentration (CIC), and ferritin for beta-Thalassemia participants
timeFrame: From Up to 5 years post CTX001 infusion (for LIC and CIC) and up to 15 years post CTX001 infusion (for ferritin)]
measure: TDT: Proportion of participants receiving iron chelation therapy over time
timeFrame: Up to 15 years post CTX001 infusion
measure: SCD: Proportion of participants who have not experienced any severe vaso-occlusive crises (VOC) for at least 12 consecutive months (VF12)
timeFrame: From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
measure: SCD: Proportion of participants with SCD free from inpatient hospitalization for severe VOCs sustained for at least 12 months (HF12)
timeFrame: From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
measure: SCD: Proportion of participants with at least 90 percent (%), 80%, 75% or 50% reduction in annualized rate of severe VOCs
timeFrame: From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
measure: SCD: Relative change from baseline in annualized rate of severe VOCs
timeFrame: From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
measure: SCD: Duration of severe VOC free in participants who have achieved VF12
timeFrame: From 60 days after last RBC transfusion up to 15 years post CTX001 infusion
measure: SCD: Relative change from baseline in rate of inpatient hospitalizations for severe VOCs
timeFrame: From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
measure: SCD: Relative change from baseline in annualized duration of hospitalization for severe VOCs
timeFrame: From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
measure: SCD: Proportion of participants with sustained HbF ≥20% for at least 3 months
timeFrame: From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
measure: SCD: Proportion of participants with sustained HbF ≥20% for at least 6 months
timeFrame: From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
measure: SCD: Proportion of participants with sustained HbF ≥20% for at least 12 months
timeFrame: From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
measure: SCD: Change in volume of RBCs transfused for SCD-related indications over time
timeFrame: Up to 15 years post CTX001 infusion
measure: SCD: Change from baseline in reticulocytes/erythrocytes over time
timeFrame: From baseline up to 15 years post CTX001 infusion
measure: SCD: Change from baseline in lactate dehydrogenase (LDH) over time
timeFrame: From baseline up to 15 years post CTX001 infusion
measure: SCD: Change from baseline in haptoglobin over time
timeFrame: From baseline up to 15 years post CTX001 infusion
measure: SCD: Change from baseline in total bilirubin over time
timeFrame: From baseline up to 15 years post CTX001 infusion
measure: SCD: Change from baseline in indirect bilirubin over time
timeFrame: From baseline up to 15 years post CTX001 infusion
measure: SCD: Change in SCD-specific PROs over time in participants ≥18 years of age assessed using adult sickle cell quality of life measurement system (ASCQ-Me) (participants from Study 121,161 and 171 only)
timeFrame: Up to 5 years post CTX001 infusion
measure: SCD: Change in SCD-specific PROs over time in participants <18 years of age assessed using PedsQL Generic Core SCD module from studies 111,121,141,151,161 and 171
timeFrame: Up to 5 years post CTX001 infusion
measure: SCD: Change in PRO over time assessed using 11-point numerical rating scale (NRS)
timeFrame: Up to 5 years post CTX001 infusion
measure: SCD: Change in PROs over time assessed using Wong Baker FACES pain scale
timeFrame: Up to 5 years post CTX001 infusion
measure: SCD: Change in PROs over time using face, legs, activity, cry, consolability (FLACC) behavioral pain scale
timeFrame: Up to 5 years post CTX001 infusion
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital
state: California
city: Chicago
country: United States
facility: Ann & Robert Lurie Children's Hospital of Chicago
state: Illinois
city: New York
country: United States
facility: Columbia University Medical Center (21+ years)
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Charlotte
country: United States
facility: Atrium Health Levine Children's Hospital
state: North Carolina
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Nashville
country: United States
facility: The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers
state: Tennessee
city: San Antonio
country: United States
facility: Methodist Healthcare System of San Antonio, Methodist Hospital, Methodist Children's Hospital
state: Texas
city: Brussels
country: Belgium
facility: Hopital Universitaire des Enfants Reine Fabiola (HUDERF)
city: Toronto
country: Canada
facility: The Hospital for Sick Children
city: Toronto
country: Canada
facility: Toronto General Hospital, University Health Network
city: Vancouver
country: Canada
facility: St. Paul's Hospital
city: Dusseldorf
country: Germany
facility: University Hospital Duesseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology
city: Regensburg
country: Germany
facility: Regensburg University Hospital, Clinic and Polyclinic for Paediatric and Adolescent Medicine
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen
city: Rome
country: Italy
facility: Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica Ospedale Pediatrico Bambino Gesu - IRCCS
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust, Hammersmith Hospital
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
Study officials:
References: