A Long-term Follow-up Study in Participants Who Received CTX001

Sickle Cell Disease Clinical Trial

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)

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04208529
• Other study ID #: CTX001-131
• Secondary ID: 2018-002935-88
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: January 20, 2021
• Est. completion date: September 2039

Study information

• Verified date: December 2023
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 160
• Est. completion date: September 2039
• Est. primary completion date: September 2039
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• beta-Thalassemia
• Genetic Diseases, Inborn
• Hematologic Diseases
• Hemoglobinopathies
• Sickle Cell Anemia
• Sickle Cell Disease
• Thalassemia

Intervention

Biological:
• CTX001
CTX001 infusion.

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto
Canada	Toronto General Hospital, University Health Network	Toronto
Canada	St. Paul's Hospital	Vancouver
Germany	University Hospital Duesseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology	Dusseldorf
Germany	Regensburg University Hospital, Clinic and Polyclinic for Paediatric and Adolescent Medicine	Regensburg
Germany	University Hospital Tuebingen	Tuebingen
Italy	Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica Ospedale Pediatrico Bambino Gesu - IRCCS	Rome
United Kingdom	Imperial College Healthcare NHS Trust, Hammersmith Hospital	London
United States	Atrium Health Levine Children's Hospital	Charlotte	North Carolina
United States	Ann & Robert Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Columbia University Medical Center (21+ years)	New York	New York
United States	Lucile Packard Children's Hospital	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Methodist Healthcare System of San Antonio, Methodist Hospital, Methodist Children's Hospital	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated	CRISPR Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	New malignancies		Signing of informed consent up to 15 years post CTX001 infusion
Primary	New or worsening hematologic disorders		Signing of informed consent up to 15 years post CTX001 infusion
Primary	All-cause mortality		Signing of informed consent up to 15 years post CTX001 infusion
Primary	Serious adverse events (SAEs)		Signing of informed consent up to 15 years post CTX001 infusion
Primary	CTX001-related adverse events (AEs)		Signing of informed consent up to 15 years post CTX001 infusion
Secondary	TDT and SCD: Total Hemoglobin (Hb) concentration over time		Up to 15 years post CTX001 infusion
Secondary	TDT and SCD: Fetal Hemoglobin (HbF) concentration over time		Up to 15 years post CTX001 infusion
Secondary	TDT and SCD: Proportion of alleles with intended genetic modification present in peripheral blood over time		Up to 15 years post CTX001 infusion
Secondary	TDT and SCD: Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time		Up to 15 years post CTX001 infusion
Secondary	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		Up to 5 years post CTX001 infusion
Secondary	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		Up to 5 years post CTX001 infusion
Secondary	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		Up to 5 years post CTX001 infusion
Secondary	TDT and SCD: Change in PROs over time in participants <18 years assessed using pediatric quality of life inventory (PedsQL) Core		Up to 5 years post CTX001 infusion
Secondary	TDT: Proportion of participants achieving transfusion independence for at least 12 consecutive months (TI12)		From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
Secondary	TDT: Proportion of participants achieving transfusion independence for at least 6 consecutive months (TI6)		From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
Secondary	TDT: Proportion of participants achieving at least 95%, 90%, 85%, 75%, 50% reduction from baseline in annualized transfusions starting 60 days after CTX001 infusion		From Day 60 up to 15 years post-CTX001 infusion
Secondary	TDT: Duration of transfusion free in participants who have achieved TI12		From 60 days after last RBC transfusion up to 15 years post CTX001 infusion
Secondary	TDT: Relative reduction from baseline in annualized volume of RBC transfusions		From Day 60 up to 15 years post-CTX001 infusion
Secondary	TDT: Iron overload as measured by liver iron concentration (LIC), cardiac iron concentration (CIC), and ferritin for beta-Thalassemia participants		From Up to 5 years post CTX001 infusion (for LIC and CIC) and up to 15 years post CTX001 infusion (for ferritin)]
Secondary	TDT: Proportion of participants receiving iron chelation therapy over time		Up to 15 years post CTX001 infusion
Secondary	SCD: Proportion of participants who have not experienced any severe vaso-occlusive crises (VOC) for at least 12 consecutive months (VF12)		From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
Secondary	SCD: Proportion of participants with SCD free from inpatient hospitalization for severe VOCs sustained for at least 12 months (HF12)		From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
Secondary	SCD: Proportion of participants with at least 90 percent (%), 80%, 75% or 50% reduction in annualized rate of severe VOCs		From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
Secondary	SCD: Relative change from baseline in annualized rate of severe VOCs		From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
Secondary	SCD: Duration of severe VOC free in participants who have achieved VF12		From 60 days after last RBC transfusion up to 15 years post CTX001 infusion
Secondary	SCD: Relative change from baseline in rate of inpatient hospitalizations for severe VOCs		From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
Secondary	SCD: Relative change from baseline in annualized duration of hospitalization for severe VOCs		From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
Secondary	SCD: Proportion of participants with sustained HbF =20% for at least 3 months		From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
Secondary	SCD: Proportion of participants with sustained HbF =20% for at least 6 months		From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
Secondary	SCD: Proportion of participants with sustained HbF =20% for at least 12 months		From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion
Secondary	SCD: Change in volume of RBCs transfused for SCD-related indications over time		Up to 15 years post CTX001 infusion
Secondary	SCD: Change from baseline in reticulocytes/erythrocytes over time		From baseline up to 15 years post CTX001 infusion
Secondary	SCD: Change from baseline in lactate dehydrogenase (LDH) over time		From baseline up to 15 years post CTX001 infusion
Secondary	SCD: Change from baseline in haptoglobin over time		From baseline up to 15 years post CTX001 infusion
Secondary	SCD: Change from baseline in total bilirubin over time		From baseline up to 15 years post CTX001 infusion
Secondary	SCD: Change from baseline in indirect bilirubin over time		From baseline up to 15 years post CTX001 infusion
Secondary	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)		Up to 5 years post CTX001 infusion
Secondary	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		Up to 5 years post CTX001 infusion
Secondary	SCD: Change in PRO over time assessed using 11-point numerical rating scale (NRS)		Up to 5 years post CTX001 infusion
Secondary	SCD: Change in PROs over time assessed using Wong Baker FACES pain scale		Up to 5 years post CTX001 infusion
Secondary	SCD: Change in PROs over time using face, legs, activity, cry, consolability (FLACC) behavioral pain scale		Up to 5 years post CTX001 infusion