Clinical Trials/NCT03745287

NCT03745287

Completed

Phase 2

A Phase 1/2/3 Study to Evaluate the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Severe Sickle Cell Disease

Vertex Pharmaceuticals Incorporated17 sites in 7 countries63 target enrollmentNovember 27, 2018

ConditionsSickle Cell Disease Hematological Diseases Hemoglobinopathies

InterventionsCTX001

DrugsCTX001

Overview

Phase: Phase 2
Intervention: CTX001
Conditions: Sickle Cell Disease
Sponsor: Vertex Pharmaceuticals Incorporated
Enrollment: 63
Locations: 17
Primary Endpoint: Incidence of transplant-related mortality (TRM) within 100 days after CTX001 infusion
Status: Completed
Last Updated: 8 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a single-arm, open-label, multi-site, single-dose Phase 1/2/3 study in subjects with severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) using CTX001.

Registry

clinicaltrials.gov

Start Date

November 27, 2018

End Date

July 7, 2025

Last Updated

8 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Vertex Pharmaceuticals Incorporated

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Diagnosis of severe sickle cell disease as defined by:
•Documented severe sickle cell disease genotype
•History of at least two severe vaso-occlusive crisis events per year for the previous two years prior to enrollment
•Eligible for autologous stem cell transplant as per investigators judgment

Exclusion Criteria

•An available 10/10 human leukocyte antigen (HLA)-matched related donor
•Prior hematopoietic stem cell transplant (HSCT)
•Clinically significant and active bacterial, viral, fungal, or parasitic infection
•Other protocol defined inclusion/exclusion criteria may apply

Arms & Interventions

CTX001

CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Subjects will receive a single infusion of CTX001 through a central venous catheter.

Intervention: CTX001

Outcomes

Primary Outcomes

Incidence of transplant-related mortality (TRM) within 100 days after CTX001 infusion

Time Frame: Within 100 days after CTX001 infusion

Proportion of subjects with engraftment (first day of three consecutive measurements of absolute neutrophil count [ANC] ≥500/µL on three different days)

Time Frame: Within 42 days after CTX001 infusion

Time to engraftment

Time Frame: From CTX001 infusion up to 2 years after CTX001 infusion

Frequency and severity of collected adverse events (AEs)

Time Frame: From screening to 2 years after CTX001 infusion

Incidence of TRM within 1 year after CTX001 infusion

Time Frame: Within 1 year after CTX001 infusion

Proportion of subjects who have not experienced any severe vaso-occlusive crisis (VOC) for at least 12 consecutive months (VF12)

Time Frame: From 60 days after last RBC transfusion up to 2 years after CTX001 infusion

All-cause mortality

Time Frame: 2 years after mobilization

Secondary Outcomes

Change in PRO over time assessed using EQ-5D-Youth (EQ-5D-Y)(3 months up to 2 years after CTX001 infusion)
Duration of severe VOC free in subjects who have achieved VF12(From 60 days after last RBC transfusion up to 2 years after CTX001 infusion)
Proportion of subjects free from inpatient hospitalization for severe VOCs sustained for at least 12 months (HF12)(From 60 days after last RBC transfusion up to 2 years after CTX001 infusion)
Proportion of subjects who have not experienced any severe VOC for at least 9 consecutive months (VF9) any time after CTX001 infusion(From 60 days after last RBC transfusion up to 2 years after CTX001 infusion)
Proportion of subjects with 90 percent (%), 80%, 75% or 50% reduction in annualized rate of severe VOCs(From 60 days after last RBC transfusion up to 2 years after CTX001 infusion)
Relative change from baseline in annualized rate of severe VOCs(From 60 days after last RBC transfusion up to 2 years after CTX001 infusion)
Relative Change from baseline in rate of inpatient hospitalization for severe VOCs(From 60 days after last RBC transfusion up to 2 years after CTX001 infusion)
Relative change from baseline in annualized duration of hospitalization for severe VOCs(From 60 days after last RBC transfusion up to 2 years after CTX001 infusion)
Proportion of subjects with sustained HbF ≥20% for at least 12 months(From 60 days after last RBC transfusion up to 2 years after CTX001 infusion)
Proportion of subjects with sustained HbF ≥20% for at least 3 months(From 60 days after last RBC transfusion up to 2 years after CTX001 infusion)
Proportion of subjects with sustained HbF ≥20% for at least 6 months(From 60 days after last RBC transfusion up to 2 years after CTX001 infusion)
Change in number of units of RBC transfused for SCD-related indications(6 months up to 2 years after CTX001 infusion)
HbF concentration over time(1 month up to 2 years after CTX001 infusion)
Hb concentration over time(From the time of CTX001 up to 2 years after CTX001 infusion)
Change from baseline in lactate dehydrogenase over time(From baseline (pre-infusion) up to 2 years after CTX001 infusion)
Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time(1 month up to 2 years after CTX001 infusion)
Change in PRO over time assessed using adult sickle cell quality of life measurement system (ASCQ-Me)(3 months up to 2 years after CTX001 infusion)
Change from baseline in indirect bilirubin over time(From baseline (pre-infusion) up to 2 years after CTX001 infusion)
Change from baseline in reticulocyte count over time(From baseline (pre-infusion) up to 2 years after CTX001 infusion)
Change from baseline in haptoglobin over time(From baseline (pre-infusion) up to 2 years after CTX001 infusion)
Proportion of alleles with intended genetic modification present in CD34+ cells of bone marrow over time(6 months up to 2 years after CTX001 infusion)
Change in patient-reported outcome (PRO) over time assessed using weekly pain-scale (11-point numerical rating scale [NRS])(3 months up to 2 years after CTX001 infusion)
Change in PRO over time assessed using EuroQol quality of life scale (EQ-5D-5L)(3 months up to 2 years after CTX001 infusion)
Change in PRO over time assessed using functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) questionnaire(3 months up to 2 years after CTX001 infusion)
Change in PRO over time assessed using pediatric quality of life inventory (PedsQL)(3 months up to 2 years after CTX001 infusion)
Change in PRO over time assessed using PedsQL sickle cell disease module(3 months up to 2 years after CTX001 infusion)