Study on the Effectiveness and Safety of Exa-cel for Adolescents and Adults with Severe Sickle Cell Disease

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What is this study about?

This clinical trial is focused on studying the effects of a new treatment for people with severe Sickle Cell Disease, specifically those with the βS/βC genotype. The treatment being tested is called Exagamglogene Autotemcel, also known as Exa-cel. This treatment uses a technique called CRISPR-Cas9 gene editing to modify certain genes in the body, aiming to restore the natural production of a type of hemoglobin called HbF, which can help reduce the symptoms of the disease.

The purpose of the study is to evaluate the effectiveness and safety of a single dose of Exa-cel in adolescents and adults with severe Sickle Cell Disease. Participants will receive the treatment through an infusion, which is a way of delivering medication directly into the bloodstream. Before receiving Exa-cel, participants will undergo a conditioning process with a medication called Busulfan, which helps prepare the body for the new treatment. The study will monitor participants over time to see if the treatment helps reduce the number of severe pain episodes and other complications associated with the disease.

Throughout the study, researchers will keep track of various health indicators to ensure the treatment is safe and effective. This includes monitoring for any side effects, changes in blood cell levels, and overall health improvements. The study aims to provide valuable information on whether Exa-cel can be a beneficial treatment option for those living with severe Sickle Cell Disease.

1 Enrollment and Initial Assessment

Upon joining the study, confirmation of the βS/βC genotype is required. This involves a genetic test to verify the specific type of sickle cell disease.

An assessment of the severity of sickle cell disease is conducted. This includes reviewing the history of acute pain events, acute chest syndrome, priapism, and splenic sequestration over the past two years.

2 Pre-Treatment Preparation

A performance status evaluation is performed to ensure the ability to undergo treatment. This involves assessing daily living activities and overall health.

Eligibility for an autologous stem cell transplant is determined by a healthcare professional.

3 Stem Cell Mobilization

Administration of Mozobil 20 mg/ml solution for injection is given to mobilize stem cells. This medication is injected to help move stem cells from the bone marrow into the bloodstream.

4 Conditioning Treatment

Treatment with Busulfan Fresenius Kabi 6 mg/ml concentrate for solution for infusion is administered. This is an intravenous infusion used to prepare the body for the stem cell transplant by reducing the number of existing blood cells.

5 Stem Cell Transplant

Infusion of exagamglogene autotemcel is performed. This is a dispersion for infusion that introduces genetically modified stem cells back into the body to help produce healthy blood cells.

6 Post-Transplant Monitoring

Regular monitoring for adverse events and overall health is conducted. This includes checking blood counts and organ function.

Evaluation of the absence of severe vaso-occlusive crises for at least 12 consecutive months begins 60 days after the last red blood cell transfusion.

7 Long-Term Follow-Up

Participation in a long-term follow-up study or registry study is required for a total of 15 years after the exa-cel infusion. This involves periodic health assessments and monitoring of the treatment’s long-term effects.

Who Can Join the Study?

Must have a documented u03b2S/u03b2C (HbSC) genotype. This means a specific type of sickle cell disease confirmed by genetic testing.
Must have severe sickle cell disease (SCD). This is defined by having at least 2 of the following events each year for the past 2 years, even with proper care:
- Acute pain event: Severe pain that requires visiting a medical facility and getting pain medications or blood transfusions.
- Acute chest syndrome: A lung problem with symptoms like pneumonia, pain, or fever, shown by a new lung issue on an X-ray.
- Priapism: A painful erection lasting more than 2 hours that needs medical attention.
- Splenic sequestration: A condition where the spleen gets bigger, causing pain in the upper left belly and a sudden drop in hemoglobin (a part of blood) by at least 2 grams per deciliter.
Must have a Karnofsky performance status of 80% or higher if 16 years or older, or a Lansky performance status of 80% or higher if under 16. These are scales that measure how well a person can perform daily activities.
Must be eligible for an autologous stem cell transplant. This means the person can receive a transplant using their own stem cells, as decided by the study doctor.
Must be willing to participate in a long-term follow-up study or registry study for a total of 15 years after receiving the study treatment.
Must be either male or female, as both genders are eligible.

Who Cannot Join the Study?

Individuals who do not have sickle cell anaemia cannot participate. Sickle cell anaemia is a blood disorder that affects the shape of red blood cells.
Individuals who do not have the specific genetic type called βS/βC genotype (HbSC) cannot participate. This refers to a specific combination of genes related to sickle cell disease.
Individuals who are not in the age range of adolescents or adults cannot participate. This means the study is only for people who are teenagers or older.
Individuals who are part of a vulnerable population cannot participate. Vulnerable populations include groups who may need special protection or care.

Where you can join this trial?

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Verified Sites

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Other Sites

Site Name	City	Country	Status
Hopital Beaujon	Clichy	France
Ospedale Pediatrico Bambino Gesu’	Rome	Italy

Trial status

Country	Status	Recruitment Start
France	Not yet recruiting	01.11.2023
Italy	Not yet recruiting	01.11.2023

Trial locations

Investigated drugs:

Exa-cel is a medication being studied for its effectiveness and safety in treating severe sickle cell disease in patients with the HbSC genotype. This medication is given as a single dose and aims to improve the health condition of individuals suffering from this genetic blood disorder.

Investigated diseases:

Sickle cell anaemia

Sickle Cell Anemia – Sickle cell anemia is a genetic blood disorder characterized by the production of abnormal hemoglobin, known as hemoglobin S. This causes red blood cells to become rigid and shaped like a sickle, which can block blood flow in small vessels. The disease often leads to episodes of pain, known as vaso-occlusive crises, and can cause damage to organs over time. Individuals with sickle cell anemia may experience fatigue, anemia, and increased risk of infections. The condition is inherited in an autosomal recessive pattern, meaning both parents must carry the gene for a child to be affected. It is most common in people of African, Mediterranean, Middle Eastern, and Indian ancestry.

Trial ID:

2023-503247-34-00

Protocol code:

VX21-CTX001-171

Trial Phase:

Therapeutic confirmatory (Phase III)

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Study on the Effectiveness and Safety of Exa-cel for Adolescents and Adults with Severe Sickle Cell Disease

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