CTX001 for Sickle Cell Disease

No longer recruiting at 18 trial locations

Overseen By Medical Information

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Vertex Pharmaceuticals Incorporated

Disqualifiers: Prior HSCT, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CTX001 for individuals with severe sickle cell disease. The goal is to determine if this gene-editing technique is safe and effective in reducing complications. Eligible participants should have severe sickle cell disease with a history of at least two painful crises each year. The trial administers a single dose of the treatment through a catheter into the bloodstream. It aims to provide a potential new option for those experiencing frequent sickle cell crises. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering hope for a new, effective treatment option.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that CTX001 is likely to be safe for humans?

Research has shown that CTX001, a treatment for sickle cell disease, has promising safety results. Studies have found that CTX001, also known as exagamglogene autotemcel, is well-tolerated by patients. For example, four months after receiving CTX001, patients did not experience painful episodes called VOCs (vaso-occlusive crises), marking a significant improvement for those with sickle cell disease.

Moreover, the U.S. Food and Drug Administration (FDA) has approved exagamglogene autotemcel for severe sickle cell disease, indicating confidence in its safety. While all treatments can have side effects, data so far shows that CTX001 is generally safe for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for sickle cell disease, which often involve blood transfusions and hydroxyurea to manage symptoms, CTX001 offers a potentially curative approach. This treatment is unique because it uses CRISPR-Cas9 gene editing technology to modify a patient's own stem cells, targeting the BCL11A gene enhancer to increase fetal hemoglobin production. Researchers are excited about CTX001 because it addresses the root cause of sickle cell disease rather than just alleviating symptoms, which could lead to a long-term solution and significantly improve patients' quality of life.

What evidence suggests that CTX001 might be an effective treatment for sickle cell disease?

Research has shown that CTX001, the treatment under study in this trial, holds promise for treating sickle cell disease. In one study, all patients who received CTX001 experienced no painful episodes caused by sickle-shaped blood cells for at least 12 months. Additionally, these patients had higher hemoglobin levels, which are important for carrying oxygen in the blood. Another set of data demonstrated that CTX001 stopped painful episodes in all patients with sickle cell disease. These results suggest that CTX001 could effectively manage severe sickle cell disease. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for people with severe sickle cell disease, who've had at least two major pain crises a year over the last two years. They must be suitable for their own stem cell transplant but can't have an available perfect-match donor or previous transplants. Active serious infections disqualify them.

Inclusion Criteria

I have severe sickle cell disease with at least two major pain crises per year.

Exclusion Criteria

I have a perfect match for a stem cell donor and no active infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single infusion of CTX001 through a central venous catheter

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months up to 2 years

Regular visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• CTX001

Trial Overview The study tests CTX001, which uses CRISPR-Cas9 to modify patients' own blood-forming cells aiming to treat severe sickle cell disease. It's a single-arm trial where all participants receive one dose of this gene-editing therapy and are monitored for safety and effectiveness.

How Is the Trial Designed?

Group I: CTX001 Experimental Treatment 1 Intervention

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.

CTX001 is already approved in European Union, United States for the following indications:

Approved in European Union as CTX001 for:

• Transfusion-dependent β-thalassemia (TDT)
• Severe sickle cell disease (SCD)

Approved in United States as CTX001 for:

• Transfusion-dependent β-thalassemia (TDT)
• Severe sickle cell disease (SCD)

Who Is Running the Clinical Trial?

Vertex Pharmaceuticals Incorporated

Lead Sponsor

Trials

267

Recruited

36,100+

Dr. David Altshuler

Vertex Pharmaceuticals Incorporated

Chief Medical Officer since 2020

MD, PhD

Dr. Reshma Kewalramani

Vertex Pharmaceuticals Incorporated

Chief Executive Officer since 2020

MD, trained in internal medicine and nephrology

CRISPR Therapeutics

Industry Sponsor

Trials

7

Recruited

630+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03745287

A Safety and Efficacy Study Evaluating CTX001 in Subjects ... 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 ...

2. ir.crisprtx.com ir.crisprtx.com/news-releases/news-release-details/vertex-and-crispr-therapeutics-present-new-data-22-patients

Press Release Beta thalassemia: All 15 patients were transfusion independent after CTX001 infusion - - Sickle cell disease: All seven patients were free of vaso-occlusive ...

3. ashpublications.org ashpublications.org/ashclinicalnews/news/8012/Full-Results-of-Exa-Cel-Study-Show-Continued

Full Results of Exa-Cel Study Show Continued Safety, Efficacy ... The study met both its primary and secondary endpoints: of the 30 evaluable patients, 97% were free from VOCs for at least 12 consecutive months, and 100% were ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10112499/

5612617 EFFICACY AND SAFETY OF A SINGLE DOSE ... Exa-cel infusion led to elimination of transfusions in almost all patients with TDT and elimination of VOCs in all patients with SCD.

5. library.ehaweb.org library.ehaweb.org/eha/2021/eha2021-virtual-congress/325494/stephan.grupp.ctx001.for.sickle.cell.disease.safety.and.efficacy.results.from.html

CTX001 FOR SICKLE CELL DISEASE: SAFETY AND ... Early data from patients with SCD infused with CTX001 showed increased levels of total hemoglobin (Hb), HbF, and F-cell pancellularity over time ...

6. ir.crisprtx.com ir.crisprtx.com/news-releases/news-release-details/vertex-and-crispr-therapeutics-present-new-clinical-data

Press Release Abstract #EP736 entitled “CTX001 for Sickle Cell Disease: Safety and Efficacy Results from the Ongoing CLIMB SCD-121 Study of Autologous Crispr-Cas9 ...

7. sicklecelldisease.org sicklecelldisease.org/2019/11/19/crispr-therapeutics-and-vertex-announce-positive-safety-and-efficacy-data/

CRISPR Therapeutics and Vertex Announce Positive ... At four months after CTX001 infusion, the patient was free of VOCs and had total hemoglobin levels of 11.3 g/dL, 46.6% fetal hemoglobin, and ...